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BIOTECHNOLOGY (227 journals)                  1 2 | Last

Showing 1 - 200 of 227 Journals sorted alphabetically
3 Biotech     Open Access   (Followers: 7)
Advances in Bioscience and Biotechnology     Open Access   (Followers: 14)
Advances in Genetic Engineering & Biotechnology     Hybrid Journal   (Followers: 7)
African Journal of Biotechnology     Open Access   (Followers: 6)
Algal Research     Partially Free   (Followers: 9)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 69)
American Journal of Bioinformatics Research     Open Access   (Followers: 8)
American Journal of Polymer Science     Open Access   (Followers: 29)
Animal Biotechnology     Hybrid Journal   (Followers: 9)
Annales des Sciences Agronomiques     Full-text available via subscription  
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 42)
Applied Bioenergy     Open Access  
Applied Biosafety     Hybrid Journal  
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 62)
Applied Mycology and Biotechnology     Full-text available via subscription   (Followers: 5)
Arthroplasty Today     Open Access   (Followers: 1)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 2)
Asia Pacific Biotech News     Hybrid Journal   (Followers: 2)
Asian Journal of Biotechnology     Open Access   (Followers: 8)
Asian Pacific Journal of Tropical Biomedicine     Open Access   (Followers: 2)
Australasian Biotechnology     Full-text available via subscription   (Followers: 1)
Banat's Journal of Biotechnology     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Bio-Algorithms and Med-Systems     Hybrid Journal   (Followers: 1)
Bio-Research     Full-text available via subscription   (Followers: 2)
Bioactive Materials     Open Access   (Followers: 1)
Biocatalysis and Agricultural Biotechnology     Hybrid Journal   (Followers: 4)
Biocybernetics and Biological Engineering     Full-text available via subscription   (Followers: 5)
Bioethics UPdate     Hybrid Journal  
Biofuels     Hybrid Journal   (Followers: 11)
Biofuels Engineering     Open Access   (Followers: 1)
Biological & Pharmaceutical Bulletin     Full-text available via subscription   (Followers: 5)
Biological Cybernetics     Hybrid Journal   (Followers: 10)
Biomarkers and Genomic Medicine     Open Access   (Followers: 5)
Biomarkers in Drug Development     Partially Free   (Followers: 1)
Biomaterials Research     Open Access   (Followers: 4)
BioMed Research International     Open Access   (Followers: 6)
Biomédica     Open Access  
Biomedical Engineering Research     Open Access   (Followers: 7)
Biomedical glasses     Open Access  
Biomedical Reports     Full-text available via subscription  
BioMedicine     Open Access  
Bioprinting     Hybrid Journal  
Bioresource Technology Reports     Hybrid Journal  
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 22)
Biosimilars     Open Access   (Followers: 1)
Biosurface and Biotribology     Open Access  
Biotechnic and Histochemistry     Hybrid Journal   (Followers: 2)
BioTechniques : The International Journal of Life Science Methods     Full-text available via subscription   (Followers: 28)
Biotechnologia Acta     Open Access   (Followers: 1)
Biotechnologie, Agronomie, Société et Environnement     Open Access   (Followers: 2)
Biotechnology     Open Access   (Followers: 6)
Biotechnology & Biotechnological Equipment     Open Access   (Followers: 5)
Biotechnology Advances     Hybrid Journal   (Followers: 33)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 161)
Biotechnology and Bioprocess Engineering     Hybrid Journal   (Followers: 6)
Biotechnology and Genetic Engineering Reviews     Hybrid Journal   (Followers: 14)
Biotechnology and Health Sciences     Open Access   (Followers: 1)
Biotechnology and Molecular Biology Reviews     Open Access   (Followers: 1)
Biotechnology Annual Review     Full-text available via subscription   (Followers: 7)
Biotechnology for Biofuels     Open Access   (Followers: 10)
Biotechnology Frontier     Open Access   (Followers: 2)
Biotechnology Journal     Hybrid Journal   (Followers: 15)
Biotechnology Law Report     Hybrid Journal   (Followers: 4)
Biotechnology Letters     Hybrid Journal   (Followers: 33)
Biotechnology Progress     Hybrid Journal   (Followers: 39)
Biotechnology Reports     Open Access  
Biotechnology Research International     Open Access   (Followers: 2)
Biotechnology Techniques     Hybrid Journal   (Followers: 10)
Biotecnología Aplicada     Open Access  
Biotribology     Hybrid Journal  
BMC Biotechnology     Open Access   (Followers: 15)
Chinese Journal of Agricultural Biotechnology     Full-text available via subscription   (Followers: 3)
Communications in Mathematical Biology and Neuroscience     Open Access  
Computational and Structural Biotechnology Journal     Open Access   (Followers: 2)
Computer Methods and Programs in Biomedicine     Hybrid Journal   (Followers: 8)
Contributions to Tobacco Research     Open Access   (Followers: 3)
Copernican Letters     Open Access   (Followers: 1)
Critical Reviews in Biotechnology     Hybrid Journal   (Followers: 20)
Crop Breeding and Applied Biotechnology     Open Access   (Followers: 4)
Current Bionanotechnology     Hybrid Journal  
Current Biotechnology     Hybrid Journal   (Followers: 3)
Current Opinion in Biomedical Engineering     Hybrid Journal   (Followers: 1)
Current Opinion in Biotechnology     Hybrid Journal   (Followers: 55)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 9)
Current Research in Bioinformatics     Open Access   (Followers: 14)
Current trends in Biotechnology and Pharmacy     Open Access   (Followers: 9)
EBioMedicine     Open Access  
Electronic Journal of Biotechnology     Open Access   (Followers: 1)
Entomologia Generalis     Full-text available via subscription  
Environmental Science : Processes & Impacts     Full-text available via subscription   (Followers: 4)
Experimental Biology and Medicine     Hybrid Journal   (Followers: 3)
Folia Medica Indonesiana     Open Access  
Food Bioscience     Hybrid Journal  
Food Biotechnology     Hybrid Journal   (Followers: 12)
Food Science and Biotechnology     Hybrid Journal   (Followers: 9)
Frontiers in Bioengineering and Biotechnology     Open Access   (Followers: 6)
Frontiers in Systems Biology     Open Access   (Followers: 2)
Fungal Biology and Biotechnology     Open Access   (Followers: 1)
GM Crops and Food: Biotechnology in Agriculture and the Food Chain     Full-text available via subscription   (Followers: 1)
GSTF Journal of BioSciences     Open Access  
HAYATI Journal of Biosciences     Open Access  
Horticulture, Environment, and Biotechnology     Hybrid Journal   (Followers: 11)
IEEE Transactions on Molecular, Biological and Multi-Scale Communications     Hybrid Journal   (Followers: 1)
IET Nanobiotechnology     Hybrid Journal   (Followers: 2)
IIOAB Letters     Open Access  
IN VIVO     Full-text available via subscription   (Followers: 4)
Indian Journal of Biotechnology (IJBT)     Open Access   (Followers: 2)
Indonesia Journal of Biomedical Science     Open Access   (Followers: 1)
Indonesian Journal of Biotechnology     Open Access   (Followers: 1)
Industrial Biotechnology     Hybrid Journal   (Followers: 18)
International Biomechanics     Open Access  
International Journal of Bioinformatics Research and Applications     Hybrid Journal   (Followers: 15)
International Journal of Biomechatronics and Biomedical Robotics     Hybrid Journal   (Followers: 4)
International Journal of Biomedical Research     Open Access   (Followers: 2)
International Journal of Biotechnology     Hybrid Journal   (Followers: 5)
International Journal of Biotechnology and Molecular Biology Research     Open Access   (Followers: 2)
International Journal of Biotechnology for Wellness Industries     Partially Free   (Followers: 1)
International Journal of Environment, Agriculture and Biotechnology     Open Access   (Followers: 5)
International Journal of Functional Informatics and Personalised Medicine     Hybrid Journal   (Followers: 4)
International Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
International Journal of Nanotechnology and Molecular Computation     Full-text available via subscription   (Followers: 3)
International Journal of Radiation Biology     Hybrid Journal   (Followers: 4)
Iranian Journal of Biotechnology     Open Access  
ISABB Journal of Biotechnology and Bioinformatics     Open Access  
Italian Journal of Food Science     Open Access   (Followers: 1)
Journal of Biometrics & Biostatistics     Open Access   (Followers: 3)
Journal of Bioterrorism & Biodefense     Open Access   (Followers: 6)
Journal of Petroleum & Environmental Biotechnology     Open Access   (Followers: 2)
Journal of Advanced Therapies and Medical Innovation Sciences     Open Access  
Journal of Advances in Biotechnology     Open Access   (Followers: 5)
Journal Of Agrobiotechnology     Open Access  
Journal of Analytical & Bioanalytical Techniques     Open Access   (Followers: 7)
Journal of Animal Science and Biotechnology     Open Access   (Followers: 6)
Journal of Applied Biomedicine     Open Access   (Followers: 3)
Journal of Applied Biotechnology     Open Access   (Followers: 2)
Journal of Applied Biotechnology Reports     Open Access   (Followers: 2)
Journal of Applied Mathematics & Bioinformatics     Open Access   (Followers: 5)
Journal of Biologically Active Products from Nature     Hybrid Journal   (Followers: 1)
Journal of Biomaterials and Nanobiotechnology     Open Access   (Followers: 6)
Journal of Biomedical Photonics & Engineering     Open Access  
Journal of Biomedical Practitioners     Open Access  
Journal of Bioprocess Engineering and Biorefinery     Full-text available via subscription  
Journal of Bioprocessing & Biotechniques     Open Access  
Journal of Biosecurity, Biosafety and Biodefense Law     Hybrid Journal   (Followers: 3)
Journal of Biotechnology     Hybrid Journal   (Followers: 68)
Journal of Chemical and Biological Interfaces     Full-text available via subscription   (Followers: 1)
Journal of Chemical Technology & Biotechnology     Hybrid Journal   (Followers: 10)
Journal of Chitin and Chitosan Science     Full-text available via subscription  
Journal of Colloid Science and Biotechnology     Full-text available via subscription  
Journal of Commercial Biotechnology     Full-text available via subscription   (Followers: 6)
Journal of Crop Science and Biotechnology     Hybrid Journal   (Followers: 7)
Journal of Essential Oil Research     Hybrid Journal   (Followers: 3)
Journal of Experimental Biology     Full-text available via subscription   (Followers: 25)
Journal of Genetic Engineering and Biotechnology     Open Access   (Followers: 5)
Journal of Ginseng Research     Open Access  
Journal of Industrial Microbiology and Biotechnology     Hybrid Journal   (Followers: 16)
Journal of Integrative Bioinformatics     Open Access  
Journal of International Biotechnology Law     Hybrid Journal   (Followers: 3)
Journal of Medical Imaging and Health Informatics     Full-text available via subscription  
Journal of Molecular Microbiology and Biotechnology     Full-text available via subscription   (Followers: 14)
Journal of Nano Education     Full-text available via subscription  
Journal of Nanobiotechnology     Open Access   (Followers: 4)
Journal of Nanofluids     Full-text available via subscription   (Followers: 2)
Journal of Organic and Biomolecular Simulations     Open Access  
Journal of Plant Biochemistry and Biotechnology     Hybrid Journal   (Followers: 6)
Journal of Science and Applications : Biomedicine     Open Access  
Journal of the Mechanical Behavior of Biomedical Materials     Hybrid Journal   (Followers: 11)
Journal of Trace Elements in Medicine and Biology     Hybrid Journal   (Followers: 1)
Journal of Tropical Microbiology and Biotechnology     Full-text available via subscription  
Journal of Yeast and Fungal Research     Open Access   (Followers: 1)
Marine Biotechnology     Hybrid Journal   (Followers: 5)
Messenger     Full-text available via subscription  
Metabolic Engineering Communications     Open Access   (Followers: 4)
Metalloproteinases In Medicine     Open Access  
Microalgae Biotechnology     Open Access   (Followers: 2)
Microbial Biotechnology     Open Access   (Followers: 9)
MicroMedicine     Open Access   (Followers: 3)
Molecular and Cellular Biomedical Sciences     Open Access  
Molecular Biotechnology     Hybrid Journal   (Followers: 16)
Molecular Genetics and Metabolism Reports     Open Access   (Followers: 3)
Nanobiomedicine     Open Access  
Nanobiotechnology     Hybrid Journal   (Followers: 3)
Nanomaterials and Nanotechnology     Open Access  
Nanomaterials and Tissue Regeneration     Open Access  
Nanomedicine and Nanobiology     Full-text available via subscription  
Nanomedicine Research Journal     Open Access  
Nanotechnology Reviews     Hybrid Journal   (Followers: 5)
Nature Biotechnology     Full-text available via subscription   (Followers: 520)
Network Modeling and Analysis in Health Informatics and Bioinformatics     Hybrid Journal   (Followers: 3)
New Biotechnology     Hybrid Journal   (Followers: 4)
Nigerian Journal of Biotechnology     Open Access  
Nova Biotechnologica et Chimica     Open Access  
NPG Asia Materials     Open Access  
npj Biofilms and Microbiomes     Open Access  
OA Biotechnology     Open Access  
Plant Biotechnology Journal     Open Access   (Followers: 10)
Plant Biotechnology Reports     Hybrid Journal   (Followers: 4)
Preparative Biochemistry and Biotechnology     Hybrid Journal   (Followers: 4)

        1 2 | Last

Journal Cover Molecular Genetics and Metabolism Reports
  [SJR: 0.344]   [H-I: 3]   [3 followers]  Follow
  This is an Open Access Journal Open Access journal
   ISSN (Print) 2214-4269
   Published by Elsevier Homepage  [3177 journals]
  • High incidence of low vitamin B12 levels in Estonian newborns

    • Authors: Karit Reinson; Kadi Künnapas; Annika Kriisa; Mari-Anne Vals; Kai Muru; Katrin Õunap
      Pages: 1 - 5
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Karit Reinson, Kadi Künnapas, Annika Kriisa, Mari-Anne Vals, Kai Muru, Katrin Õunap
      Vitamin B12 deficiency seems to be more common worldwide than previously thought. However, only a few reports based on data from newborn screening (NBS) programs have drawn attention to that subject. In Estonia, over the past three years, we have diagnosed 14 newborns with congenital acquired vitamin B12 deficiency. Therefore, the incidence of that condition is 33.8/100,000 live births, which is considerably more than previously believed. None of the newborns had any clinical symptoms associated with vitamin B12 deficiency before the treatment, and all biochemical markers normalized after treatment, which strongly supports the presence of treatable congenital deficiency of vitamin B12. During the screening period, we began using actively ratios of some metabolites like propionylcarnitine (C3) to acetylcarnitine (C2) and C3 to palmitoylcarnitine (C16) to improve the identification of newborns with acquired vitamin B12 deficiency. In the light of the results obtained, we will continue to screen the congenital acquired vitamin B12 deficiency among our NBS program. Every child with aberrant C3, C3/C2 and C3/C16 will be thoroughly examined to exclude acquired vitamin B12 deficiency, which can easily be corrected in most cases.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2017.11.002
      Issue No: Vol. 15 (2018)
  • The impact of consanguinity on the frequency of inborn errors of

    • Authors: Raja Majid Afzal; Allan Meldgaard Lund; Flemming Skovby
      Pages: 6 - 10
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Raja Majid Afzal, Allan Meldgaard Lund, Flemming Skovby
      Inborn errors of metabolism (IEM) are a heterogeneous group of genetic disorders present in all ethnic groups. We investigated the frequency of consanguinity among parents of newborns with IEM diagnosed by neonatal screening. Data were obtained from 15years of expanded newborn screening for selected IEM with autosomal recessive mode of inheritance, a national screening program of newborns covering the period from 2002 until April 2017. Among the 838,675 newborns from Denmark, the Faroe Islands and Greenland, a total of 196 newborns had an IEM of whom 155 from Denmark were included in this study. These results were crosschecked against medical records. Information on consanguinity was extracted from medical records and telephone contact with the families. Among ethnic Danes, two cases of consanguinity were identified in 93 families (2.15%). Among ethnic minorities there were 20 cases of consanguinity among 33 families (60.6%). Consequently, consanguinity was 28.2 times more frequent among descendants of other geographic place of origin than Denmark. The frequency of consanguinity was conspicuously high among children of Pakistani, Afghan, Turkish and Arab origin (71.4%). The overall frequency of IEM was 25.5 times higher among children of Pakistani, Turkish, Afghan and Arab origin compared to ethnic Danish children (5.35:10,000 v 0.21:10,000). The frequency of IEM was 30-fold and 50-fold higher among Pakistanis (6.5:10,000) and Afghans (10.6:10,000), respectively, compared to ethnic Danish children. The data indicate a strong association between consanguinity and IEM. These figures could be useful to health professionals providing antenatal, pediatric, and clinical genetic services.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2017.11.004
      Issue No: Vol. 15 (2018)
  • Type 1 sialidosis presenting with ataxia, seizures and myoclonus with no
           visual involvement

    • Authors: Ahmed N. Mohammad; Katelyn A. Bruno; S. Hines; Paldeep S. Atwal
      Pages: 11 - 14
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Ahmed N. Mohammad, Katelyn A. Bruno, S. Hines, Paldeep S. Atwal
      Sialidosis is an autosomal recessive lysosomal storage disease caused by pathogenic variants in NEU1 which encodes lysosomal sialidase (neuraminidase 1). Lysosomal neuraminidase catalyzes the removal of terminal sialic acid molecules from glycolipids, glycoproteins and oligosaccharides. Sialidosis is classified into two types, based on phenotype and age of onset. Patients with the milder type 1 typically present late, usually in the second or third decade, with myoclonus, ataxia and visual defects. Type 2 is more severe and presents earlier with coarse facial features, developmental delay, hepatosplenomegaly and dysostosis multiplex. Presentation and severity of the disease are related to whether lysosomal sialidase is inactive or there is some residual activity. Diagnosis is suspected based on clinical features and increased urinary bound sialic acid excretion and confirmed by genetic testing showing pathogenic variants in NEU1. We report a patient with type 1 sialidosis who presented mainly with ataxia and both generalized and myoclonic seizures but no visual involvement. Whole exome sequencing of the proband detected compound heterozygous likely pathogenic variants (S182G and G227R) in NEU1.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2017.12.005
      Issue No: Vol. 15 (2018)
  • S-adenosylhomocysteine hydrolase over-expression does not alter
           S-adenosylmethionine or S-adenosylhomocysteine levels in CBS deficient

    • Authors: Hyung-Ok Lee; Liqun Wang; Yin-Ming Kuo; Andrew J. Andrews; Sapna Gupta; Warren D. Kruger
      Pages: 15 - 21
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Hyung-Ok Lee, Liqun Wang, Yin-Ming Kuo, Andrew J. Andrews, Sapna Gupta, Warren D. Kruger
      Elevated plasma total homocysteine (tHcy) is associated with a number of human diseases including coronary artery disease, stroke, osteoporosis and dementia. It is highly correlated with intracellular S-adenosylhomocysteine (SAH). Since SAH is a strong inhibitor of methyl-transfer reactions involving the methyl-donor S-adenosylmethionine (SAM), elevation in SAH could be an explanation for the wide association of tHcy and human disease. Here, we have created a transgenic mouse (Tg-hAHCY) that expresses human S-adenosylhomocysteine hydrolase (AHCY) from a zinc-inducible promoter in the liver and kidney. Protein analysis shows that human AHCY is expressed well in both liver and kidney, but elevated AHCY enzyme activity (131% increase) is only detected in the kidney due to the high levels of endogenous mouse AHCY expression in liver. Tg-hAHCY mice were crossed with mice lacking cystathionine β-synthase activity (Tg-I278T Cbs −/− ) to explore the effect to AHCY overexpression in the context of elevated serum tHcy and elevated tissue SAM and SAH. Overexpression of AHCY had no significant effect on the phenotypes of Tg-I278T Cbs −/− mice or any effect on the steady state concentrations of methionine, total homocysteine, SAM, SAH, and SAM/SAH ratio in the liver and kidney. Furthermore, enhanced AHCY activity did not lower serum and tissue tHcy or methionine levels. Our data suggests that enhancing AHCY activity does not alter the distribution of methionine recycling metabolites, even when they are greatly elevated by Cbs mutations.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.002
      Issue No: Vol. 15 (2018)
  • Natural history of children and adults with maple syrup urine disease in
           the NBS-MSUD Connect registry

    • Authors: Aileen Kenneson; Yetsa Osara; Theresa Pringle; Lauren Youngborg; Rani H. Singh
      Pages: 22 - 27
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Aileen Kenneson, Yetsa Osara, Theresa Pringle, Lauren Youngborg, Rani H. Singh

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.001
      Issue No: Vol. 15 (2018)
  • Phenotypic variability of MTO1-deficiency

    • Authors: Josef Finsterer; Sinda Zarrouk-Mahjoub
      Pages: 28 - 29
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.003
      Issue No: Vol. 15 (2018)
  • Sex differences in body composition and bone mineral density in
           phenylketonuria: A cross-sectional study

    • Authors: Bridget M. Stroup; Karen E. Hansen; Diane Krueger; Neil Binkley; Denise M. Ney
      Pages: 30 - 35
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Bridget M. Stroup, Karen E. Hansen, Diane Krueger, Neil Binkley, Denise M. Ney
      Background Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). Objective To determine if there are differences in BMD and body composition between male and female participants with PKU. Methods From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15–50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16–35y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1–3weeks each. Results Male participants had significantly lower mean total body BMD Z-scores (means±SE, males=−0.9±0.4; females, 0.2±0.3; p =0.01) and tended to have lower mean L1–4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above −1.0 compared to 100% of females (p =0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r =−0.58; p =0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means±SE, males: 67±6g, females: 52±4g; p =0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339±75mg/d, females: 228±69mg/d; p =0.13). Females had a greater percentage of total fat mass compared to males (means±SE, males: 24.5±4.8%, females: 36.5±2.5%; p =0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. Conclusions Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at as NCT01428258.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.004
      Issue No: Vol. 15 (2018)
  • Effects of cold exposure on metabolites in brown adipose tissue of rats

    • Authors: Yuka Hiroshima; Takenori Yamamoto; Masahiro Watanabe; Yoshinobu Baba; Yasuo Shinohara
      Pages: 36 - 42
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Yuka Hiroshima, Takenori Yamamoto, Masahiro Watanabe, Yoshinobu Baba, Yasuo Shinohara
      Brown adipose tissue (BAT) plays an important role in regulation of energy expenditure while adapting to a cold environment. BAT thermogenesis depends on uncoupling protein 1 (UCP1), which is expressed in the inner mitochondrial membranes of BAT. Gene expression profiles induced by cold exposure in BAT have been studied, but the metabolomic biological pathway that contributes to the activation of thermogenesis in BAT remains unclear. In this study, we comprehensively compared the relative levels of metabolites between the BAT of rats kept at room temperature (22 °C) and of those exposed to a cold temperature (4 °C) for 48 h using capillary electrophoresis (CE) time-of-flight mass spectrometry (TOFMS) and liquid chromatography (LC)-TOFMS. We identified 218 metabolites (137 cations and 81 anions) by CE-TOFMS and detected 81 metabolites (47 positive and 34 negative) by LC-TOFMS in BAT. We found that cold exposure highly influenced the BAT metabolome. We showed that the cold environment lead to lower levels of glycolysis and gluconeogenesis intermediates and higher levels of the tricarboxylic acid (TCA) cycle metabolites, fatty acids, and acyl-carnitine metabolites than control conditions in the BAT of rats. These results indicate that glycolysis and β-oxidation of fatty acids in BAT are positive biological pathways that contribute to the activation of thermogenesis by cold exposure, thereby facilitating the generation of heat by UCP1. These data provide useful information for understanding the basal metabolic functions of BAT thermogenesis in rats in response to cold exposure.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.005
      Issue No: Vol. 15 (2018)
  • An atypical p.N215S variant of Fabry disease with end-stage renal failure

    • Authors: Max Sugarman; Jamil Choudhury; Ana Jovanovic
      Pages: 43 - 45
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Max Sugarman, Jamil Choudhury, Ana Jovanovic
      Fabry disease is an X-linked metabolic disorder resulting in widespread deposition of Globotriaosylceramide within a variety of human tissues. The classical Fabry phenotype is one of early onset disease, with extensive tissue involvement resulting in acroparaesthesia, gastrointestinal disturbances, angiokeratoma, cornea verticillata renal failure, and cardiovascular disease. We describe two brothers exhibiting the GLA p.N215S mutation, a variant most often conferring a late-onset disease confined to the myocardium. The proband was diagnosed aged 34, following investigation into proteinuria. Despite Enzyme Replacement Therapy, he progressed to end-stage renal failure, and subsequently received a renal transplant. He also developed hypertrophic cardiomyopathy. His sibling however, whose disease was detected aged 32 following screening, exhibits mild left ventricular hypertrophy, and no evidence of renal disease. He remains clinically asymptomatic. This case report details a discordant phenotype in brothers with Fabry disease and p.N215S mutation. Despite the fact that in the majority of patients this mutation is associated with a late onset presentation with hypertrophic cardiomyopathy, we have clearly demonstrated that patients with GLA p.N215S mutation can present with the classical phenotype. Further studies are required to elucidate the underlying modifying factors that influence clinical presentation with a more severe phenotype.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.006
      Issue No: Vol. 15 (2018)
  • Hyperphosphatasia with mental retardation syndrome, expanded phenotype of
           PIGL related disorders

    • Authors: Ruqaiah Altassan; Stephanie Fox; Chantal Poulin; Daniela Buhas
      Pages: 46 - 49
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Ruqaiah Altassan, Stephanie Fox, Chantal Poulin, Daniela Buhas
      Hypomorphic mutations in six different genes involved in the glycosylphosphatidylinositol (GPI) biogenesis pathway are linked to Mabry syndrome (hyperphosphatasia with mental retardation syndrome, HPMRS). This report on the third affected family with a HPMRS phenotype caused by mutations in PIGL, confirming the seventh GPI biogenesis gene linked to HPMRS. Two siblings presented with the main features of HPMRS; developmental delay, cognitive impairment, seizure disorder, skeletal deformities, and high alkaline phosphatase. We identified two heterozygous mutations in the PIGL gene (P.Trp20Ter and p.Arg88Cys). PIGL mutations have been linked to another distinctive neuroectodermal disorder: CHIME syndrome. The clinical picture of our patients expands the spectrum of PIGL-related phenotypes.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.01.007
      Issue No: Vol. 15 (2018)
  • The phenotype, genotype, and outcome of infantile-onset Pompe disease in
           18 Saudi patients

    • Authors: Zuhair N. Al-Hassnan; Ola A. Khalifa; Dalal K. Bubshait; Sahar Tulbah; Maarab Alkorashy; Hamad Alzaidan; Mohammed Alowain; Zuhair Rahbeeni; Moeen Al-Sayed
      Pages: 50 - 54
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Zuhair N. Al-Hassnan, Ola A. Khalifa, Dalal K. Bubshait, Sahar Tulbah, Maarab Alkorashy, Hamad Alzaidan, Mohammed Alowain, Zuhair Rahbeeni, Moeen Al-Sayed
      Infantile-Onset Pompe Disease (IOPD) is an autosomal recessive disorder of glycogen metabolism resulting from deficiency of the lysosomal hydrolase acid α-glucosidase encoded by GAA gene. Affected infants present before the age of 12 months with hypotonia, muscle weakness, and hypertrophic cardiomyopathy. Enzyme replacement therapy (ERT) has been shown to improve survival, cardiac mass, and motor skills. In this work, we aim to illustrate the genotypes of IOPD and the outcome of ERT in our population. The medical records of infants with confirmed diagnosis of IOPD who received ERT were reviewed. Eighteen infants (7 males, 11 females) were included in the study. The median age at presentation was 2 months and the median age at the start of ERT was 4.5 months. Fifteen (83.3%) infants died with a median age at death of 12 months. The 3 alive infants (whose current ages are 6½ years, 6 years, and 10 years), who were initiated on ERT at the age of 3 weeks, 5 months, and 8 months respectively, has had variable response with requirement of assisted ventilation in one child and tracheostomy in another child. All infants were homozygous for GAA mutations except one infant who was compound heterozygous. All infants (n = 8) with truncating mutations died. Our work provides insight into the correlation of genotypes and outcome of ERT in IOPD in Saudi Arabia. Our data suggest that early detection of cases, through newborn screening, and immunomodulation before the initiation of ERT may improve the outcome of ERT in Saudi infants with IOPD.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.02.001
      Issue No: Vol. 15 (2018)
  • Open-label clinical trial of bezafibrate treatment in patients with fatty
           acid oxidation disorders in Japan

    • Authors: Kenji Yamada; Hideaki Shiraishi; Eishin Oki; Mika Ishige; Toshiyuki Fukao; Yusuke Hamada; Norio Sakai; Fumihiro Ochi; Asami Watanabe; Sanae Kawakami; Kazuyo Kuzume; Kenji Watanabe; Koji Sameshima; Kiyotaka Nakamagoe; Akira Tamaoka; Naoko Asahina; Saki Yokoshiki; Takashi Miyakoshi; Kota Ono; Koji Oba; Toshiyuki Isoe; Hiroshi Hayashi; Seiji Yamaguchi; Norihiro Sato
      Pages: 55 - 63
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Kenji Yamada, Hideaki Shiraishi, Eishin Oki, Mika Ishige, Toshiyuki Fukao, Yusuke Hamada, Norio Sakai, Fumihiro Ochi, Asami Watanabe, Sanae Kawakami, Kazuyo Kuzume, Kenji Watanabe, Koji Sameshima, Kiyotaka Nakamagoe, Akira Tamaoka, Naoko Asahina, Saki Yokoshiki, Takashi Miyakoshi, Kota Ono, Koji Oba, Toshiyuki Isoe, Hiroshi Hayashi, Seiji Yamaguchi, Norihiro Sato
      Introduction Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. Materials and methods This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2 years; ranging from 5.8 to 26.4 years). Bezafibrate was administered for 6 months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16 + C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). Results The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. Conclusion In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.02.003
      Issue No: Vol. 15 (2018)
  • Clinicopathological features associated with the BAG3-Pro209Leu mutation

    • Authors: A. Schänzer; S. Rupp; B. Garvalov; A. Hahn
      First page: 64
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): A. Schänzer, S. Rupp, B. Garvalov, A. Hahn

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.02.004
      Issue No: Vol. 15 (2018)
  • BAG3-related myofibrillar myopathy requiring heart transplantation for
           restrictive cardiomyopathy

    • Authors: Josef Finsterer; Sinda Zarrouk-Mahjoub
      Pages: 65 - 66
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.02.002
      Issue No: Vol. 15 (2018)
  • A beneficial effect of l-arginine for stroke-like episodes is currently

    • Authors: Josef Finsterer; Sinda Zarrouk-Mahjoub
      Pages: 67 - 68
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.02.006
      Issue No: Vol. 15 (2018)
  • Recurrent rhabdomyolysis caused by carnitine palmitoyltransferase II
           deficiency, common but under-recognised: Lessons to be learnt

    • Authors: M. Balasubramanian; T.M. Jenkins; R.J. Kirk; I.M. Nesbitt; S.E. Olpin; M. Hill; G.T. Gillett
      Pages: 69 - 70
      Abstract: Publication date: June 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 15
      Author(s): M. Balasubramanian, T.M. Jenkins, R.J. Kirk, I.M. Nesbitt, S.E. Olpin, M. Hill, G.T. Gillett
      We discuss two adult siblings who presented with symptoms of myalgia and rhabdomyolysis following exercise with myoglobinuria; genetic testing confirmed carnitine palmitoyltransferase II deficiency and resulted in institution of appropriate crisis management and dietary advice. We explore the phenotypic variability of this commonest fatty oxidation defect that remains under-diagnosed in the adult population and provide clues for early recognition and diagnosis.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2018.02.008
      Issue No: Vol. 15 (2018)
  • A molecular analysis of the GAA gene and clinical spectrum in 38 patients
           with Pompe disease in Japan

    • Authors: Yasuyuki Fukuhara; Naoko Fuji; Narutoshi Yamazaki; Asami Hirakiyama; Tetsuharu Kamioka; Joo-Hyun Seo; Ryuichi Mashima; Motomichi Kosuga; Torayuki Okuyama
      Pages: 3 - 9
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Yasuyuki Fukuhara, Naoko Fuji, Narutoshi Yamazaki, Asami Hirakiyama, Tetsuharu Kamioka, Joo-Hyun Seo, Ryuichi Mashima, Motomichi Kosuga, Torayuki Okuyama
      Pompe disease is an autosomal recessive disorder caused by acid α-glucosidase (GAA) deficiency, which results in the accumulation of glycogen in lysosomes in multiple tissues, including cardiac, skeletal, and smooth muscle cells. Thus far, 558 sequence variants of the GAA gene have been published in the Pompe Disease Mutation Database, and some mutations appear with considerable frequency in particular ethnic groups, such as Caucasians, Taiwanese, Chinese, and Koreans. However, the GAA mutation pattern in Japanese patients remains poorly understood. We analyzed the relationship between the genetic and clinical features of 38 mostly Japanese patients with Pompe disease from 35 unrelated families. We identified 28 different GAA gene mutations, including 7 novel mutations, by a GAA gene analysis. c.546G>T (22.9%) and c.1857C>G (14.3%) were the most common mutations and accounted for 37.1% of the total mutant alleles. In the six patients with infantile-onset Pompe disease (IOPD), c.1857C>G was also the most common mutation. In addition, there were 13 homozygotes (5 with the c.546G>T) among the 35 families, which is the highest frequency reported thus far. Regarding the initial symptoms, cardiomegaly was the most common (3/6=50%) in IOPD patients, while muscle weakness was observed the most frequently in patients with late-onset Pompe disease (LOPD) (15/30=50%). Notably, all IOPD patients who showed respiratory distress at the time of onset require respiratory assistance at present (4/4=100%). Regarding the presenting symptoms, cardiomegaly (6/6=100%) and hepatomegaly (4/6=66.7%) were more commonly seen in IOPD, and muscle weakness (24/29=82.7%) was observed more frequently in LOPD. Respiratory assistance is required at present in 33.3% of IOPD patients and 50% of LOPD patients, and 20% of IOPD patients and 29.6% of LOPD patients are wheelchair users. These individual clinical courses may be influenced by the timing of the diagnosis and treatment; for example, in 2007, an ERT orphan drug for treatment of Pompe disease, Alglucosidase alfa, was made available in Japan, and there were 5 (5/6=83.3%) wheelchair users diagnosed from 2008 to 2009 (cases 32–38) and 4 (4/27=14.8%) from 2010 to 2015 (cases 1–31). These findings underscore the importance of the early diagnosis and treatment.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.10.009
      Issue No: Vol. 14 (2018)
  • Quantification of the enzyme activities of iduronate-2-sulfatase,
           N-acetylgalactosamine-6-sulfatase and N-acetylgalactosamine-4-sulfatase
           using liquid chromatography-tandem mass spectrometry

    • Authors: Ryuichi Mashima; Mari Ohira; Torayuki Okuyama; Akiya Tatsumi
      Pages: 36 - 40
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Ryuichi Mashima, Mari Ohira, Torayuki Okuyama, Akiya Tatsumi
      Mucopolysaccharidosis (MPS) is a genetic disorder characterized by the accumulation of glycosaminoglycans in the body. Of the multiple MPS disease subtypes, several are caused by defects in sulfatases. Specifically, a defect in iduronate-2-sulfatase (ID2S) leads to MPS II, whereas N-acetylgalactosamine-6-sulfatase (GALN) and N-acetylgalactosamine-4-sulfatase (ARSB) defects relate to MPS IVA and MPS VI, respectively. A previous study reported a combined assay for these three disorders in a 96-well plate using a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based technique (Kumar et al., Clin Chem 2015 61(11):1363-1371). In our study, we applied this methodology to a Japanese population to examine the assay precision and the separation of populations between disease-affected individuals and controls for these three disorders. Within our assay conditions, the coefficient of variation (CV, %) values for an interday assay of ID2S, GALN, and ARSB were 9%, 18%, and 9%, respectively (n =7). The average enzyme activities of ID2S, GALN, and ARSB in random neonates were 19.6±5.8, 1.7±0.7, and 13.4±5.2μmol/h/L (mean±SD, n =240), respectively. In contrast, the average enzyme activities of ID2S, GALN, and ARSB in disease-affected individuals were 0.5±0.2 (n =6), 0.3±0.1 (n =3), and 0.3 (n =1) μmol/h/L, respectively. The representative analytical range values corresponding to ID2S, GALN, and ARSB were 39, 17, and 168, respectively. These results raise the possibility that the population of disease-affected individuals could be separated from that of healthy individuals using the LC-MS/MS-based technique.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.12.001
      Issue No: Vol. 14 (2018)
  • Homocystinuria due to cystathionine beta-synthase (CBS) deficiency in
           Russia: Molecular and clinical characterization

    • Authors: Elena Voskoboeva; Alla Semyachkina; Maria Yablonskaya; Ekaterina Nikolaeva
      Pages: 47 - 54
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Elena Voskoboeva, Alla Semyachkina, Maria Yablonskaya, Ekaterina Nikolaeva
      We present the results of the 45-year clinical observation of 27 Russian homocystinuria patients. We made a mutation analysis of the CBS gene for thirteen patients from eleven unrelated genealogies. All patients except for the two were compound heterozygotes for the mutations detected. The most frequent mutation in the cohort investigated was splice mutation IVS11-2a->c. We detected one new nonsense mutation, one new missense-mutation and three novel small deletions. We also report the clinical case of the B6-responsive patient genotyped as Ile278Thr/Cys109Arg.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.11.001
      Issue No: Vol. 14 (2018)
  • Mildly elevated succinylacetone and normal liver function in compound
           heterozygotes with pathogenic and pseudodeficient FAH alleles

    • Authors: Hao Yang; Francis Rossignol; Denis Cyr; Rachel Laframboise; Shu Pei Wang; Jean-François Soucy; Marie-Thérèse Berthier; Yves Giguère; Paula J. Waters; Grant A. Mitchell
      Pages: 55 - 58
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Hao Yang, Francis Rossignol, Denis Cyr, Rachel Laframboise, Shu Pei Wang, Jean-François Soucy, Marie-Thérèse Berthier, Yves Giguère, Paula J. Waters, Grant A. Mitchell
      Background A high level of succinylacetone (SA) in blood is a sensitive, specific marker for the screening and diagnosis of hepatorenal tyrosinemia (HT1, MIM 276700). HT1 is caused by mutations in the FAH gene, resulting in deficiency of fumarylacetoacetate hydrolase. HT1 newborns are usually clinically asymptomatic, but have coagulation abnormalities revealing liver dysfunction. Treatment with nitisinone (NTBC) plus dietary restriction of tyrosine and phenylalanine prevents the complications of HT1 Observations Two newborns screened positive for SA but had normal coagulation testing. Plasma and urine SA levels were 3–5 fold above the reference range but were markedly lower than in typical HT1. Neither individual received nitisinone or dietary therapy. They remain clinically normal, currently aged 9 and 15years. Each was a compound heterozygote, having a splicing variant in trans with a prevalent “pseudodeficient” FAH allele, c.1021C>T (p.Arg341Trp), which confers partial FAH activity. All newborns identified with mild hypersuccinylacetonemia in Québec have had genetic deficiencies of tyrosine degradation: either deficiency of the enzyme preceding FAH, maleylacetoacetate isomerase, or partial deficiency of FAH itself. Conclusion Compound heterozygotes for c.1021C>T (p.Arg341Trp) and a severely deficient FAH allele have mild hypersuccinylacetonemia and to date they have remained asymptomatic without treatment. It is important to determine the long term outcome of such individuals.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.12.002
      Issue No: Vol. 14 (2018)
  • Characteristics of 26 patients with type 3 Gaucher disease: A descriptive
           analysis from the Gaucher Outcome Survey

    • Authors: Ida Vanessa D. Schwartz; Özlem Göker-Alpan; Priya S. Kishnani; Ari Zimran; Lydie Renault; Zoya Panahloo; Patrick Deegan
      Pages: 73 - 79
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Ida Vanessa D. Schwartz, Özlem Göker-Alpan, Priya S. Kishnani, Ari Zimran, Lydie Renault, Zoya Panahloo, Patrick Deegan
      The Gaucher Outcome Survey (GOS) is an international disease-specific registry established in 2010 for patients with a confirmed diagnosis of Gaucher disease (GD), regardless of GD type or treatment status. Historically, there has been a limited understanding of type 3 GD (GD3) and its natural history in patients irrespective of their treatment status. Here, we describe the disease characteristics of patients with GD3 enrolled in GOS. As of October 2015, 1002 patients had been enrolled, 26 of whom were reported as GD3. The majority of patients with GD3 were from the US (13; 50.0%), seven (26.9%) were from the UK, three (11.5%) from Israel, and three (11.5%) from Brazil. No patients were of Ashkenazi Jewish origin. Median age of symptom onset was 1.4 (interquartile range: 0.5–2.0) years. The most common GBA1 mutation genotype was L444P/L444P, occurring in 16 (69.6%) of 23 patients who had genotyping information available. Nine patients reported a family history of GD (any type). Of 21 patients with treatment status information, 20 (95.2%) had received GD-specific treatment at any time, primarily imiglucerase (14 patients) and/or velaglucerase alfa (13 patients). Hemoglobin concentrations and platelet counts at GOS entry were within normal ranges for most patients, and there were no reports of severe hepatomegaly or of splenomegaly in non-splenectomized patients, most likely indicative of the effects of treatment received prior to GOS entry. This analysis provides information on the characteristics of patients with GD3 that could be used as the baseline for longitudinal follow-up of these patients.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.10.011
      Issue No: Vol. 14 (2018)
  • Blood phenylalanine instability strongly correlates with anxiety in

    • Authors: Bozena Didycz; Miroslaw Bik-Multanowski
      Pages: 80 - 82
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Bozena Didycz, Miroslaw Bik-Multanowski
      We assessed the relationship between anxiety and long-term metabolic control in adolescents with phenylketonuria (PKU). We used a standardized psychological test to measure anxiety level and analyzed lifelong blood phenylalanine stability in a selected group of 25 PKU teenagers with treatment adherence problems. We demonstrated significant correlations of anxiety with variability of blood phenylalanine concentrations and with severity of hyperphenylalaninemia. Avoiding blood phenylalanine fluctuations in childhood can probably reduce anxiety in PKU adolescents.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.12.003
      Issue No: Vol. 14 (2018)
  • Dietary practices in propionic acidemia: A European survey

    • Authors: A. Daly; A. Pinto; S. Evans; M.F. Almeida; M. Assoun; A. Belanger-Quintana; S.M. Bernabei; S. Bollhalder; D. Cassiman; H. Champion; H. Chan; J. Dalmau; F. de Boer; C. de Laet; A. de Meyer; A. Desloovere; A. Dianin; M. Dixon; K. Dokoupil; S. Dubois; F. Eyskens; A. Faria; I. Fasan; E. Favre; F. Feillet; A. Fekete; G. Gallo; C. Gingell; J. Gribben; K. Kaalund Hansen; N.M. Ter Horst; C. Jankowski; R. Janssen-Regelink; I. Jones; C. Jouault; G.E. Kahrs; I.L. Kok; A. Kowalik; C. Laguerre; S. Le Verge; R. Lilje; C. Maddalon; D. Mayr; U. Meyer; A. Micciche; U. Och; M. Robert; J.C. Rocha; H. Rogozinski; C. Rohde; K. Ross; I. Saruggia; A. Schlune; K. Singleton; E. Sjoqvist; R. Skeath; L.H. Stolen; A. Terry; C. Timmer; L. Tomlinson; A. Tooke; K. Vande Kerckhove; E. van Dam; T. van den Hurk; L. van der Ploeg; M. van Driessche; M. van Rijn; A. van Wegberg; C. Vasconcelos; H. Vestergaard; I. Vitoria; D. Webster; F.J. White; L. White; H. Zweers; A. MacDonald
      Pages: 83 - 89
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): A. Daly, A. Pinto, S. Evans, M.F. Almeida, M. Assoun, A. Belanger-Quintana, S.M. Bernabei, S. Bollhalder, D. Cassiman, H. Champion, H. Chan, J. Dalmau, F. de Boer, C. de Laet, A. de Meyer, A. Desloovere, A. Dianin, M. Dixon, K. Dokoupil, S. Dubois, F. Eyskens, A. Faria, I. Fasan, E. Favre, F. Feillet, A. Fekete, G. Gallo, C. Gingell, J. Gribben, K. Kaalund Hansen, N.M. Ter Horst, C. Jankowski, R. Janssen-Regelink, I. Jones, C. Jouault, G.E. Kahrs, I.L. Kok, A. Kowalik, C. Laguerre, S. Le Verge, R. Lilje, C. Maddalon, D. Mayr, U. Meyer, A. Micciche, U. Och, M. Robert, J.C. Rocha, H. Rogozinski, C. Rohde, K. Ross, I. Saruggia, A. Schlune, K. Singleton, E. Sjoqvist, R. Skeath, L.H. Stolen, A. Terry, C. Timmer, L. Tomlinson, A. Tooke, K. Vande Kerckhove, E. van Dam, T. van den Hurk, L. van der Ploeg, M. van Driessche, M. van Rijn, A. van Wegberg, C. Vasconcelos, H. Vestergaard, I. Vitoria, D. Webster, F.J. White, L. White, H. Zweers, A. MacDonald
      Background The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. Aim To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. Methods This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. Results Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n=38) of centres, providing a median of 44% (14–83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0–6m, 7–12m, 1–10 y, 11–16 y and >16y. Sixty-three per cent (n=117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. Conclusions There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

      PubDate: 2018-01-03T23:47:00Z
      DOI: 10.1016/j.ymgmr.2017.09.002
      Issue No: Vol. 13 (2018)
  • A Letter from Brian Berman, President, National Gaucher Foundation

    • Abstract: Publication date: Available online 12 February 2018
      Source:Molecular Genetics and Metabolism Reports

      PubDate: 2018-03-07T01:29:25Z
  • ATP1A3 de novo and compound heterozygous NLRP3 mutations in a child with
           Autism Spectrum Disorder, fatigue/sleep-wake cycle/behavioral disorder,
           Muckle-Wells syndrome and psychotic-like symptoms responsive to
           antipsychotic treatment

    • Authors: Alcy Torres; Catherine A. Brownstein; Sahil K. Tembulkar; Kelsey Graber; Casie Genetti; Robin J. Kleiman; Kathleen Sweadner; Kevin X. Liu; Chrystal Mavros; Niklas Smedemark-Margulies; Pankaj B. Agrawal; Jiahai Shi; Alan H. Beggs; Eugene D'Angelo; Sarah Hope Lincoln; Devon Carroll; Fatma Dedeoglu; William A. Gahl; Catherine Biggs; Kathryn J. Swoboda; Gerard T. Berry; Joseph Gonzalez-Heydrich
      Abstract: Publication date: Available online 12 February 2018
      Source:Molecular Genetics and Metabolism Reports
      Author(s): Alcy Torres, Catherine A. Brownstein, Sahil K. Tembulkar, Kelsey Graber, Casie Genetti, Robin J. Kleiman, Kathleen Sweadner, Kevin X. Liu, Chrystal Mavros, Niklas Smedemark-Margulies, Pankaj B. Agrawal, Jiahai Shi, Alan H. Beggs, Eugene D'Angelo, Sarah Hope Lincoln, Devon Carroll, Fatma Dedeoglu, William A. Gahl, Catherine Biggs, Kathryn J. Swoboda, Gerard T. Berry, Joseph Gonzalez-Heydrich
      Complex phenotypes may be due to novel syndromes, or may be a combination of several genetic factors. Here we describe an 8-year old male with high functioning Autism Spectrum Disorder and Muckle-Wells syndrome who at age 5years reported hearing voices which described his emotions. His fixation on superhero fantasies led to injury, aggression, and interference with functioning at home and at school. These symptoms resolved with antipsychotic treatment at age 7years. After age 6, he developed intermittent episodes of fatigue and somnolence that lasted from hours to weeks and persisted despite antipsychotic treatment. Whole exome sequencing showed three mutations in genes potentially involved in his clinical phenotype. The patient has a predicted pathogenic de novo heterozygous p.Ala681Thr mutation in the ATP1A3 gene (chr19:42480621C>T, GRCh37/hg19). Mutations in this gene are known to cause Alternating Hemiplegia of Childhood, Rapid Onset Dystonia Parkinsonism, and CAPOS syndrome sometimes accompanied by autistic features. The patient also has compound heterozygosity for p.Arg490Lys/p.Val200Met mutations in the NLRP3 gene (chr1:247588214G>A and chr1:247587343G>A, respectively). NLRP3 mutations are associated in an autosomal dominant manner with clinically overlapping autoinflammatory conditions including Muckle-Wells syndrome. The p.Arg490Lys is a known pathogenic mutation inherited from the patient's father. The p.Val200Met mutation, inherited from his mother, is a variant of unknown significance (VUS). We hypothesize that the de novo ATP1A3 mutation is responsible for the patient's Autism Spectrum Disorder, psychotic-like symptoms, and fatigue/sleep-wake cycle/behavioral disorder. The unprecedented combination of two NLRP3 mutations may be responsible for the other aspects of his complex phenotype.

      PubDate: 2018-03-07T01:29:25Z
      DOI: 10.1016/j.ymgmr.2017.03.001
  • Fibroblast growth-factor-21 is currently a weak biomarker for identifying
           mitochondrial and non-mitochondrial inborn errors of metabolism

    • Authors: Josef Finsterer; Sinda Zarrouk-Mahjoub
      Pages: 1 - 2
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Josef Finsterer, Sinda Zarrouk-Mahjoub

      PubDate: 2017-10-29T01:10:02Z
      DOI: 10.1016/j.ymgmr.2017.10.005
      Issue No: Vol. 14 (2017)
  • The influence of parental food preference and neophobia on children with
           phenylketonuria (PKU)

    • Authors: Sharon Evans; Anne Daly; Satnam Chahal; Catherine Ashmore; John MacDonald; Anita MacDonald
      Pages: 10 - 14
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Sharon Evans, Anne Daly, Satnam Chahal, Catherine Ashmore, John MacDonald, Anita MacDonald
      Background In a previous case-control study, we demonstrated that children with PKU and non-PKU controls preferred sweet foods. Additionally, children with PKU exhibited food neophobia, with no preference for bitter tasting foods associated with the taste of phenylalanine (Phe)-free L-amino acid supplements. Objective In an observational extension study, we evaluated the influence of parental food choice and neophobia on their children's taste preferences and food neophobia. Methods Male and female parents/caregivers of 35 children with PKU and 35 control parents, completed a neophobia and food frequency questionnaire for comparison using the same questionnaires that they completed for their children. Results Both groups of children (PKU and non PKU control) were rated as more food neophobic and exhibited more neophobic behaviour than parents, although children with PKU more so than non-PKU controls (PKU food neophobia p<0.0001vs control 0.001; PKU general neophobia p=0.003 vs control p=0.04). Both groups of children ate significantly more sweets, sweetened drinks and potato fries than their parents but differences were greater for children with PKU who also consumed more high carbohydrate (low protein) staple foods such as bread and pasta, and more sweet snacks such as biscuits than their parents. Non-PKU control children's food choices were closer to their parent's choices. Conclusions In PKU, parental food choices and their food neophobia have limited influence on their children's eating habits. Food neophobia in children with PKU may be associated with fear of eating unfamiliar foods potentially containing a source of protein or aspartame. Their preference for sweet foods may be influenced by limited food choices and habitual consumption of artificially sweetened L-amino acid supplements.

      PubDate: 2017-11-05T03:07:10Z
      DOI: 10.1016/j.ymgmr.2017.10.007
      Issue No: Vol. 14 (2017)
  • Home infusion with Elosulfase alpha (VimizimR) in a UK Paediatric setting

    • Authors: Niamh Finnigan; Jane Roberts; Jean Mercer; Simon A. Jones
      Pages: 15 - 18
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Niamh Finnigan, Jane Roberts, Jean Mercer, Simon A. Jones
      Enzyme replacement therapy is the only available treatment for Mucopolysaccharidosis type IVA (MPS IVA, Morquio syndrome). The treatment is lengthy and invasive involving weekly intravenous infusions of 4–5h. This can cause significant disruption to normal family life so the provision of a safe and effective homecare service is essential. In order to deliver a safe service, robust standards must be in place; this includes appropriately trained members of homecare staff, detailed management for infusion related reactions (IRR) and appropriate venous access. In this report we demonstrate the criteria required to ensure a successful home treatment programme and describe our experience thus far.

      PubDate: 2017-11-05T03:07:10Z
      DOI: 10.1016/j.ymgmr.2017.10.012
      Issue No: Vol. 14 (2017)
  • Only some patients with bulbar and spinal muscular atrophy may develop
           cardiac disease

    • Authors: Josef Finsterer; Claudia Stöllberger
      Pages: 19 - 21
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Josef Finsterer, Claudia Stöllberger
      Objectives According to recent publications, some patients with spinal and bulbar muscular atrophy (BSMA) develop cardiac disease, manifesting as ST-segment abnormalities, Brugada-syndrome, dilative cardiomyopathy, or sudden cardiac death. Here we present neurological and cardiac data of a BSMA patient who was followed up for 10y. Case report In a male patient aged 47y, BSMA was diagnosed at age 37y upon the typical clinical presentation (postural tremor since age 12y, dysarthria since age 15y, muscle cramps since age 29y, general myalgias since age 32y, general fasciculations since age 34y, myoclonic jerks, easy fatigability, dyspnea upon exercise since age 36y) and a CAG-repeat expansion of 47±1 repeats in the androgen-receptor gene detected at age 37y. During the next 10y he additionally developed mild but slowly progressive diffuse weakness on the upper limbs and mild proximal weakness on the lower limbs. Cardiologic exam, ECG, and echocardiography were normal at ages 37y, 41y, 44y, and 47y. Conclusions Cardiac involvement may only develop in some BSMA patients within 10y, whereas neurologic abnormalities slowly progress within 10y of observation. Cardiac disease may develop at a later stage with progression of age and disease.

      PubDate: 2017-12-26T20:53:02Z
      DOI: 10.1016/j.ymgmr.2017.10.010
      Issue No: Vol. 14 (2017)
  • Only some patients with bulbar and spinal muscular atrophy may develop
           cardiac disease

    • Authors: Josef Finsterer; Claudia Stöllberger
      Pages: 19 - 21
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Josef Finsterer, Claudia Stöllberger
      Objectives According to recent publications, some patients with spinal and bulbar muscular atrophy (BSMA) develop cardiac disease, manifesting as ST-segment abnormalities, Brugada-syndrome, dilative cardiomyopathy, or sudden cardiac death. Here we present neurological and cardiac data of a BSMA patient who was followed up for 10y. Case report In a male patient aged 47y, BSMA was diagnosed at age 37y upon the typical clinical presentation (postural tremor since age 12y, dysarthria since age 15y, muscle cramps since age 29y, general myalgias since age 32y, general fasciculations since age 34y, myoclonic jerks, easy fatigability, dyspnea upon exercise since age 36y) and a CAG-repeat expansion of 47±1 repeats in the androgen-receptor gene detected at age 37y. During the next 10y he additionally developed mild but slowly progressive diffuse weakness on the upper limbs and mild proximal weakness on the lower limbs. Cardiologic exam, ECG, and echocardiography were normal at ages 37y, 41y, 44y, and 47y. Conclusions Cardiac involvement may only develop in some BSMA patients within 10y, whereas neurologic abnormalities slowly progress within 10y of observation. Cardiac disease may develop at a later stage with progression of age and disease.

      PubDate: 2017-11-12T05:34:03Z
      DOI: 10.1016/j.ymgmr.2017.10.010
      Issue No: Vol. 14 (2017)
  • Enzyme replacement therapy in perinatal hypophosphatasia: Case report of a
           negative outcome and lessons for clinical practice

    • Authors: Gregory Costain; Aideen M. Moore; Lauren Munroe; Alison Williams; Randi Zlotnik Shaul; Cheryl Rockman-Greenberg; Martin Offringa; Peter Kannu
      Pages: 22 - 26
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Gregory Costain, Aideen M. Moore, Lauren Munroe, Alison Williams, Randi Zlotnik Shaul, Cheryl Rockman-Greenberg, Martin Offringa, Peter Kannu
      Enzyme replacement therapy (ERT) is a newly approved disease-modifying treatment for hypophosphatasia (HPP), a rare metabolic bone disorder. With an orphan drug and ultra-rare disease, sharing information about responders and non-responders is particularly important, as any one centre's familiarity with its use will be limited. Nearly all published data in infants and very young children with life-threatening HPP are from three small clinical trials that have reported generally positive outcomes. We describe in detail a patient with perinatal HPP for whom treatment with ERT was not successful. Lessons learned from this case can inform clinical decision-making and provide topics for the research agenda. We also discuss practical and ethical challenges related to treatment of an ultra-rare disease with an expensive new medication in a publicly funded healthcare system.

      PubDate: 2017-11-12T05:34:03Z
      DOI: 10.1016/j.ymgmr.2017.10.006
      Issue No: Vol. 14 (2017)
  • Parkinson's disease prevalence in Fabry disease: A survey study

    • Authors: Adina H. Wise; Amy Yang; Hetanshi Naik; Chanan Stauffer; Natasha Zeid; Christopher Liong; Manisha Balwani; Robert J. Desnick; Roy N. Alcalay
      Pages: 27 - 30
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Adina H. Wise, Amy Yang, Hetanshi Naik, Chanan Stauffer, Natasha Zeid, Christopher Liong, Manisha Balwani, Robert J. Desnick, Roy N. Alcalay
      Recent research has suggested a possible link between Parkinson's disease (PD) and Fabry disease. To test this relationship, we administered a self-report and family history questionnaire to determine the prevalence of PD in Fabry disease patients and family members with likely pathogenic alpha-galactosidase A (GLA) mutations. A total of 90 Fabry patients (77 from the online survey and 13 from the Icahn School of Medicine at Mount Sinai (ISMMS)) were included in the analysis. Two of the Fabry disease patients who completed the online survey were diagnosed with PD (2/90, 2.2%). Among probands older than 60, 8.3% (2/24) were diagnosed with PD. Using Kaplan Meier survival analysis, the age-specific risk of PD by age 70 was 11.1%. Family history was available on 72 Fabry families from the online study and 9 Fabry families from ISMMS. Among these 81 families, 6 (7.4%) had one first degree relative who fit the criteria for a conservative diagnosis of PD. The results of this study suggest that there may be an increased risk of developing PD in individuals with GLA mutations, but these findings should be interpreted with caution given the limitations of the study design.

      PubDate: 2017-11-12T05:34:03Z
      DOI: 10.1016/j.ymgmr.2017.10.013
      Issue No: Vol. 14 (2017)
  • Long-term outcomes with agalsidase alfa enzyme replacement therapy:
           Analysis using deconstructed composite events

    • Authors: Michael Beck; Derralynn Hughes; Christoph Kampmann; Guillem Pintos-Morell; Uma Ramaswami; Michael L. West; Roberto Giugliani
      Pages: 31 - 35
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Michael Beck, Derralynn Hughes, Christoph Kampmann, Guillem Pintos-Morell, Uma Ramaswami, Michael L. West, Roberto Giugliani
      This is a retrospective analysis of Fabry Outcome Survey data from children/adults (n =677) receiving agalsidase alfa enzyme replacement therapy for a median of 3years, examining cerebrovascular, cardiac, and renal morbidity endpoints separately. Cardiac events occurred at younger ages than cerebrovascular or renal events, cerebrovascular events were more frequent in females than males, and males were more likely to experience cardiac and renal events at a younger age than females.

      PubDate: 2017-11-12T05:34:03Z
      DOI: 10.1016/j.ymgmr.2017.10.008
      Issue No: Vol. 14 (2017)
  • Phenotypic spectrum of FARS2-deficiency

    • Authors: Josef Finsterer; Carla A. Scorza; Fulvio A. Scorza
      Pages: 41 - 42
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Josef Finsterer, Carla A. Scorza, Fulvio A. Scorza

      PubDate: 2017-12-26T20:53:02Z
      DOI: 10.1016/j.ymgmr.2017.11.003
      Issue No: Vol. 14 (2017)
  • Motor involvement in Fabry disease

    • Authors: Sirio Cocozza; Lorenzo Ugga; Giuseppe Pontillo; Camilla Russo; Enrico Tedeschi; Antonio Pisani; Arturo Brunetti
      First page: 43
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Sirio Cocozza, Lorenzo Ugga, Giuseppe Pontillo, Camilla Russo, Enrico Tedeschi, Antonio Pisani, Arturo Brunetti

      PubDate: 2017-12-26T20:53:02Z
      DOI: 10.1016/j.ymgmr.2017.11.006
      Issue No: Vol. 14 (2017)
  • Natural history of Morquio A patient with tracheal obstruction from birth
           to death

    • Authors: Caitlin Doherty; Lauren W. Averill; Mary Theroux; William G. Mackenzie; Christian Pizarro; Robert W. Mason; Shunji Tomatsu
      Pages: 59 - 67
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Caitlin Doherty, Lauren W. Averill, Mary Theroux, William G. Mackenzie, Christian Pizarro, Robert W. Mason, Shunji Tomatsu
      Morquio A syndrome (mucopolysaccharidosis IVA, MPS IVA) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase, resulting in systemic accumulation of the partially degraded glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate. The accumulation of these GAGs leads to distinguishing features as skeletal dysplasia with disproportionate dwarfism, short neck, kyphoscoliosis, pectus carinatum, tracheal obstruction, coxa valga, genu valgum, and joint laxity. In the absence of autopsied cases and systemic analysis of multiple tissues, the pathological mechanism of the characteristic skeletal dysplasia associated with the disease largely remains a question. Here we report an autopsied case of a 23-year-old male with MPS IVA, who developed characteristic skeletal abnormalities by 4months of age and died of severe tracheal obstruction and hypoventilation originating from respiratory muscle weakness from neurological cord deficit due to cord myelopathy at the age of 23. We analyzed postmortem tissues pathohistologically, including the thyroid, lung, lung bronchus, trachea, heart, aorta, liver, spleen, kidney, testes, humerus, knee cartilage, and knee ligament. Examination of the tissues demonstrated systemic storage materials in multiple tissues, as well as severely ballooned and vacuolated chondrocytes in the trachea, humerus, knee cartilage, and lung bronchus. This autopsied case with MPS IVA addresses the importance of tracheal obstruction for morbidity and mortality of the disease, and the pathological findings contribute to a further understanding of the pathogenesis of MPS IVA and the development of novel therapies.

      PubDate: 2017-12-26T20:53:02Z
      DOI: 10.1016/j.ymgmr.2017.11.005
      Issue No: Vol. 14 (2017)
  • Ten-year-long enzyme replacement therapy shows a poor effect in
           alleviating giant leg ulcers in a male with Fabry disease

    • Authors: Jun Okada; Mohammad Arif Hossain; Chen Wu; Takashi Miyajima; Hiroko Yanagisawa; Keiko Akiyama; Yoshikatsu Eto
      Pages: 68 - 72
      Abstract: Publication date: March 2018
      Source:Molecular Genetics and Metabolism Reports, Volume 14
      Author(s): Jun Okada, Mohammad Arif Hossain, Chen Wu, Takashi Miyajima, Hiroko Yanagisawa, Keiko Akiyama, Yoshikatsu Eto
      Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of α-galactosidase A (α-gal A), leading to the progressive accumulation of glycosphingolipids. Classical hemizygous males usually present symptoms, including pain and paresthesia in the extremities, angiokeratoma, hypo- or anhidrosis, abdominal pain, cornea verticillata, early stroke, tinnitus, and/or hearing loss, during early childhood or adolescence. Moreover, proteinuria, renal impairment, and cardiac hypertrophy can appear with age. Enzyme replacement is the most common therapy for Fabry disease at present which has been approved in Japan since 2004. We report a case involving a 27-year-old male with extreme terminal pain, anhidrosis, abdominal pain, tinnitus, hearing impairment, cornea verticillata, and recurrent huge ulcers in the lower extremities. At the age of 16years, he was diagnosed with Fabry disease with a positive family history and very low α-gal A activity. He then received enzyme replacement therapy (ERT) with recombinant human agalsidase beta at 1mg/kg every 2weeks for 10years. Throughout the course of ERT, his leg ulcers recurred, and massive excretion of urinary globotriaosylceramide and plasma globotriaosylsphingosine was observed. Electron microscopy of the venous tissue in the regions of the ulcer showed massive typical zebra bodies in the vascular wall smooth muscle cells.

      PubDate: 2017-12-26T20:53:02Z
      DOI: 10.1016/j.ymgmr.2017.12.004
      Issue No: Vol. 14 (2017)
  • Type 3 Gaucher disease, diagnostic in adulthood

    • Authors: Charles Detollenaere; Monia Benghergbia; Anaïs Brassier; Thierry Billette de Villemeur; Daniel Amsallem; Marc Berger; Jérôme Stirnemann; Nadia Belmatoug; Christian Rose
      Pages: 1 - 2
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Charles Detollenaere, Monia Benghergbia, Anaïs Brassier, Thierry Billette de Villemeur, Daniel Amsallem, Marc Berger, Jérôme Stirnemann, Nadia Belmatoug, Christian Rose

      PubDate: 2017-07-14T04:57:04Z
      DOI: 10.1016/j.ymgmr.2017.07.002
      Issue No: Vol. 13 (2017)
  • Lipid profile in adult patients with Fabry disease - Ten-year follow up

    • Authors: Karolina M. Stepien; Chris J. Hendriksz
      Pages: 3 - 6
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Karolina M. Stepien, Chris J. Hendriksz
      Background Fabry disease, an X-linked genetic condition, results from alpha-galactosidase deficiency and increased accumulation of glycosphingolipids in cardiovascular tissues. Clinical manifestation includes vasculature associated complications. Hyperlipidaemia is one of the cardiovascular risk factors however it has never been well defined in Fabry disease. Enzyme Replacement Therapy (ERT) is available but its effect on serum cholesterol is unknown. The aim of this project was to assess the influence of long-term ERT on lipid profile in a large cohort of adult patients with Fabry disease. Methods This was a retrospective analysis of lipid profile results. Patients with Fabry disease were on ERT for 10years, were not treated with statins and had no severe renal impairment. All patients had lipid profile measured before ERT was commenced and 6, 12, 24, 36, 48, 60, 120months later. Statistical analysis included ANOVA, Student t-test and descriptive statistics. Results Among 72 patients, 40 were females (median age 45; range 29–75), 32 males (median age 46; range 20–69). There was no significant difference in total cholesterol or HDL-cholesterol measured at baseline before ERT was commenced and 6, 12, 24, 36, 48, 60 and 120months after ERT was commenced in 72 patients (ANOVA; P =0.673 and P =0.883, respectively). Female patients on ERT had higher mean HDL-cholesterol as compared to female patients with Fabry disease who were asymptomatic and not treated (P ≥0.05). Total cholesterol between treated and non-treated female patients was comparable. Female patients on ERT have higher total cholesterol and HDL-cholesterol when compared to lipid results in male patients on ERT. Total cholesterol/HDL-cholesterol ratio was low in female and male patients on ERT over 10years. Conclusion Adult patients with Fabry disease have remarkably elevated HDL-cholesterol and as a result, elevated total cholesterol. It is possible that elevated HDL-cholesterol has a cardioprotective effect in patients with this condition. Long term ERT does not have a significant impact on lipid profile in female and male population with Fabry disease.

      PubDate: 2017-07-14T04:57:04Z
      DOI: 10.1016/j.ymgmr.2017.06.010
      Issue No: Vol. 13 (2017)
  • A novel nonsense ATP7A pathogenic variant in a family exhibiting a
           variable occipital horn syndrome phenotype

    • Authors: Maria Teresa Bonati; Federico Verde; Uros Hladnik; Paola Cattelan; Luca Campana; Chiara Castronovo; Nicola Ticozzi; Luca Maderna; Claudia Colombrita; Sergio Papa; Paolo Banfi; Vincenzo Silani
      Pages: 14 - 17
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Maria Teresa Bonati, Federico Verde, Uros Hladnik, Paola Cattelan, Luca Campana, Chiara Castronovo, Nicola Ticozzi, Luca Maderna, Claudia Colombrita, Sergio Papa, Paolo Banfi, Vincenzo Silani
      We report on a family with occipital horn syndrome (OHS) diagnosed in the proband's late fifties. A novel ATP7A pathogenic variant (c.4222A>T, p.(Lys1408*)), representing the first nonsense variant and the second late truncation causing OHS rather than classic Menkes disease, was found to segregate in the family. The predicted maintenance of transmembrane domains is consistent with a residual protein activity, which may explain the mild clinical presentation.

      PubDate: 2017-07-24T08:27:41Z
      DOI: 10.1016/j.ymgmr.2017.07.007
      Issue No: Vol. 13 (2017)
  • A pilot study on using rapamycin-carrying synthetic vaccine particles
           (SVP) in conjunction with enzyme replacement therapy to induce immune
           tolerance in Pompe disease

    • Authors: Han-Hyuk Lim; Haiqing Yi; Takashi K. Kishimoto; Fengqin Gao; Baodong Sun; Priya S. Kishnani
      Pages: 18 - 22
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Han-Hyuk Lim, Haiqing Yi, Takashi K. Kishimoto, Fengqin Gao, Baodong Sun, Priya S. Kishnani
      A major obstacle to enzyme replacement therapy (ERT) with recombinant human acid-α-glucosidase (rhGAA) for Pompe disease is the development of high titers of anti-rhGAA antibodies in a subset of patients, which often leads to a loss of treatment efficacy. In an effort to induce sustained immune tolerance to rhGAA, we supplemented the rhGAA therapy with a weekly intravenous injection of synthetic vaccine particles carrying rapamycin (SVP-Rapa) during the first 3weeks of a 12-week course of ERT in GAA-KO mice, and compared this with three intraperitoneal injections of methotrexate (MTX) per week for the first 3weeks. Empty nanoparticles (NP) were used as negative control for SVP-Rapa. Co-administration of SVP-Rapa with rhGAA resulted in more durable inhibition of anti-rhGAA antibody responses, higher efficacy in glycogen clearance in skeletal muscles, and greater improvement of motor function than mice treated with empty NP or MTX. Body weight loss was observed during the MTX-treatment but not SVP-Rapa-treatment. Our data suggest that co-administration of SVP-Rapa may be an innovative and safe strategy to induce durable immune tolerance to rhGAA during the ERT in patients with Pompe disease, leading to improved clinical outcomes.

      PubDate: 2017-07-24T08:27:41Z
      DOI: 10.1016/j.ymgmr.2017.03.005
      Issue No: Vol. 13 (2017)
  • Role of AMPD2 in impaired glucose tolerance induced by high fructose diet

    • Authors: Athanasius Wrin Hudoyo; Tetsuaki Hirase; Andreas Tandelillin; Masahiko Honda; Manabu Shirai; Jidong Cheng; Hiroko Morisaki; Takayuki Morisaki
      Pages: 23 - 29
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Athanasius Wrin Hudoyo, Tetsuaki Hirase, Andreas Tandelillin, Masahiko Honda, Manabu Shirai, Jidong Cheng, Hiroko Morisaki, Takayuki Morisaki
      A high intake of products containing fructose is known to mediate insulin resistance. In the liver, AMPD2, an isoform of AMPD, has important glucose metabolic homeostasis functions including maintenance of AMP-activated protein kinase (AMPK). We speculated that AMPD2 induces impaired glucose tolerance in individuals who consume a high-fructose diet. We gave either a normal-chow (NCD) or high-fructose (HFrD) diet for 40days to 8-week-old male wild-type (WT) and Ampd2 −/− homozygote (A2−/−) C57BL/6 mice. A glucose tolerance test (GTT) and pyruvate tolerance test (PTT) were used to evaluate glucose metabolism. In addition, gluconeogenesis and glycolysis enzymes, and AMPK phosphorylation in the liver were investigated. With consumption of the HFrD, A2−/− mice showed enhanced glucose tolerance in GTT and PTT results as compared to the WT mice, which were independent of changes in body weight. Also, the levels of phosphoenolpyruvate carboxy kinase and glucose-6-phosphatase (hepatic gluconeogenic enzymes) were significantly reduced in A2−/− as compared to WT mice. The hepatic glycolytic enzymes glucokinase, phosphofructokinase, and pyruvate kinase were also examined, though there were no significant differences between genotypes in regard to both mRNA expression and protein expression under HFrD. Surprisingly, hepatic AMPK phosphorylation resulted in no changes in the A2−/− as compared to WT mice under these conditions. Our results indicated that Ampd2–deficient mice are protected from high fructose diet-induced glycemic dysregulation, mainly because of gluconeogenesis inhibition, and indicate a novel therapeutic target for type 2 diabetes mellitus.

      PubDate: 2017-07-30T09:50:09Z
      DOI: 10.1016/j.ymgmr.2017.07.006
      Issue No: Vol. 13 (2017)
  • Limitations of galactose therapy in phosphoglucomutase 1 deficiency

    • Authors: Kristine Nolting; Julien H. Park; Laura C. Tegtmeyer; Andrea Zühlsdorf; Marianne Grüneberg; Stephan Rust; Janine Reunert; Ingrid Du Chesne; Volker Debus; Eric Schulze-Bahr; Robert C. Baxter; Yoshinao Wada; Christian Thiel; Emile van Schaftingen; Ralph Fingerhut; Thorsten Marquardt
      Pages: 33 - 40
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Kristine Nolting, Julien H. Park, Laura C. Tegtmeyer, Andrea Zühlsdorf, Marianne Grüneberg, Stephan Rust, Janine Reunert, Ingrid Du Chesne, Volker Debus, Eric Schulze-Bahr, Robert C. Baxter, Yoshinao Wada, Christian Thiel, Emile van Schaftingen, Ralph Fingerhut, Thorsten Marquardt
      Introduction Phosphoglucomutase 1 deficiency (PGM1 deficiency) has been identified as both, glycogenosis and congenital disorder of glycosylation (CDG). The phenotype includes hepatopathy, myopathy, oropharyngeal malformations, heart disease and growth retardation. Oral galactose supplementation at a dosage of 1g per kg body weight per day is regarded as the therapy of choice. Results We report on a patient with a novel disease causing mutation, who was treated for 1.5years with oral galactose supplementation. Initially, elevated transaminases were reduced and protein glycosylation of serum transferrin improved rapidly. Long-term surveillance however indicated limitations of galactose supplementation at the standard dose: 1g per kg body weight per day did not achieve permanent correction of protein glycosylation. Even increased doses of up to 2.5g per kg body weight did not result in complete normalization. Furthermore, we described for the first time heart rhythm abnormalities, i.e. long QT Syndrome associated with a glycosylation disorder. Mass spectrometry of IGFBP3, which was assumed to play a major role in growth retardation associated with PGM1 deficiency, revealed no glycosylation abnormalities. Growth rate did not improve under galactose supplementation. Conclusions The results of our study indicate that the current standard dose of galactose might be too low to achieve normal glycosylation in all patients. In addition, growth retardation in PGM1 deficiency is complex and multifactorial. Furthermore, heart rhythm abnormalities must be considered when treating patients with PGM1 deficiency.

      PubDate: 2017-08-09T14:05:11Z
      DOI: 10.1016/j.ymgmr.2017.07.010
      Issue No: Vol. 13 (2017)
  • The cardiac glycoside convallatoxin inhibits the growth of colorectal
           cancer cells in a p53-independent manner

    • Authors: Sarah E. Anderson; Christopher E. Barton
      Pages: 42 - 45
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Sarah E. Anderson, Christopher E. Barton
      Cardiac glycosides are plant-derived molecules that have shown antiproliferative properties against cancer cells, though the mechanism of action is not completely understood. We show that one cardiac glycoside, convallatoxin, presents antiproliferative effects against colorectal cancer cells in culture and that the resulting cell death is independent of the p53 tumor suppressor. Our data suggest that convallatoxin may be useful in the treatment of cancers that harbor inactivating mutations in the p53 signaling pathway.

      PubDate: 2017-08-09T14:05:11Z
      DOI: 10.1016/j.ymgmr.2017.07.011
      Issue No: Vol. 13 (2017)
  • Plasma fibroblast growth factor-21 levels in patients with inborn errors
           of metabolism

    • Authors: Brian Kirmse; Juan Cabrerra-Luque; Omar Ayyub; Kristina Cusmano; Kimberly Chapman; Marshall Summar
      Pages: 52 - 54
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Brian Kirmse, Juan Cabrerra-Luque, Omar Ayyub, Kristina Cusmano, Kimberly Chapman, Marshall Summar
      Fibroblast growth factor-21 (FGF21) levels are elevated in patients with primary mitochondrial disorders but have not been studied in patients with inborn errors of metabolism (IEM) known to have secondary mitochondrial dysfunction. We measured plasma FGF21 by ELISA in patients with and without IEM. FGF21 levels were higher in patients with IEM compared to without IEM (370pg/dL vs. 0–65pg/dL). Further study of FGF21 as a biomarker in IEM is warranted.

      PubDate: 2017-09-06T00:58:04Z
      DOI: 10.1016/j.ymgmr.2017.04.001
      Issue No: Vol. 13 (2017)
  • Neonatal screening for biotinidase deficiency: A 30-year single center

    • Authors: Francesco Porta; Veronica Pagliardini; Isabella Celestino; Enza Pavanello; Severo Pagliardini; Ornella Guardamagna; Alberto Ponzone; Marco Spada
      Pages: 80 - 82
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Francesco Porta, Veronica Pagliardini, Isabella Celestino, Enza Pavanello, Severo Pagliardini, Ornella Guardamagna, Alberto Ponzone, Marco Spada
      We reviewed the outcome of newborn screening for biotinidase deficiency performed at our department since 1987. Among 1,097,894 newborns screened, 461 were recalled, and 18 were identified as affected by complete or partial biotinidase deficiency (incidence 1:61,000, false positive rate 0.04%). The common missense mutation Q456H was found in 80% of patients with profound biotinidase deficiency. Of them, one patient harbored the novel mutation M399I in compound heterozygosity (M399I/Q456H). The complex allele A171T/D444H in cis was found in two patients with profound biotinidase deficiency (in homozygosity and in compound heterozygosity with the R211H mutation, respectively) and in one patient with partial biotinidase deficiency (in compound heterozygosity with the protective allele D444H in trans). All detected patients were treated and followed up at our Center until present. Biotin therapy (10–20mg/day) allowed the full prevention of clinical symptoms in all patients with no adverse effects. These excellent outcomes confirm that newborn screening for biotinidase deficiency is a very effective secondary prevention program.

      PubDate: 2017-09-23T06:49:57Z
      DOI: 10.1016/j.ymgmr.2017.08.005
      Issue No: Vol. 13 (2017)
  • First-year metabolic control guidelines and their impact on future
           metabolic control and neurocognitive functioning in children with PKU

    • Authors: Alicia de la Parra; María Ignacia García; Valerie Hamilton; Carolina Arias; Juan Francisco Cabello; Verónica Cornejo
      Pages: 90 - 94
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Alicia de la Parra, María Ignacia García, Valerie Hamilton, Carolina Arias, Juan Francisco Cabello, Verónica Cornejo
      There is a consensus on the importance of early and life-long treatment for PKU patients. Still, differences exist on target blood phenylalanine (Phe) concentrations for children with PKU in different countries and treatment centers. For the first time, long-term metabolic control and child development and cognitive functioning is compared between children with mean phenylalanine concentrations under 240μmol/L (group A), between 240 and 360μmol/L (group B) or over 360μmol/L (group C) during their first year of life. METHODS: 70 patients diagnosed with PKU through neonatal screening with Phe >900μmol/L, were divided into 3 groups: A, B and C, according to mean Phe concentrations and standard deviation (SD). Metabolic control during childhood, psychomotor development and IQ were compared. RESULTS: In group A, Phe was maintained within the recommended range until 6years of age, in Group B, until 3years of age, and in group C, Phe was always over the recommended range. No significant differences were found between the three groups in mental development index (MDI) and motor development index (PDI) scores at 12, 24, and 30months of age, but group C had the lowest scores on MDI at all age periods. At preschool and school age, IQ was higher in group A compared to group C. CONCLUSION: Results show that mean blood Phe concentrations between 120 and 240μmol/L during first year of life have a positive impact in metabolic control and cognitive functioning during childhood.

      PubDate: 2017-10-21T21:57:43Z
      DOI: 10.1016/j.ymgmr.2017.09.003
      Issue No: Vol. 13 (2017)
  • The use of port-a-caths in adult patients with Lysosomal Storage Disorders
           receiving Enzyme Replacement Therapy-one centre experience

    • Authors: Mairead McLoughlin; Karolina Stepien Briony McNelly Lorraine Thompson Janet Gorton
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Mairead McLoughlin, Karolina M. Stepien, Briony McNelly, Lorraine Thompson, Janet Gorton, Christian J. Hendriksz
      Port-a-cath is a widely used device in patients with long-term venous access demand such as frequent or continuous administration of medications such as Enzyme Replacement Therapy (ERT), chemotherapy delivery, blood transfusions, blood products, and fluids. Patients with Lysosomal Storage Diseases (LSDs) often require recurrent courses of ERT. We reviewed our experience of using port-a-caths in patients with LSDs with the focus on challenges and complications associated with these catheters. Among 245 adult patients who were treated with ERT, twenty patients (8.2%) had a port-a-cath inserted due to poor venous access. Six patients were using their first port whereas five other patients had their port-a-caths replaced at least once. The remaining six patients had inactive port-a-caths. The majority of patients with active port-a-caths never missed more than one consecutive infusion, although one patient missed 2 consecutive infusions whilst on holiday. We identified significant gaps in patients' and their families' understanding of the management of port-a-caths and risks associated with them. It resulted in producing a leaflet and designing an educational program for our LSD patients.

      PubDate: 2017-10-21T21:57:43Z
  • Refining low protein modular feeds for children on low protein tube feeds
           with organic acidaemias

    • Authors: Daly Evans; Ashmore Chahal Santra MacDonald
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): A. Daly, S. Evans, C. Ashmore, S. Chahal, S. Santra, A. MacDonald
      Children with inherited metabolic disorders (IMD) who are dependent on tube feeding and require a protein restriction are commonly fed by ‘modular tube feeds’ consisting of several ingredients. A longitudinal, prospective two-phase study, conducted over 18months assessed the long-term efficacy of a pre-measured protein-free composite feed. This was specifically designed to meet the non-protein nutritional requirements of children (aged over 1year) with organic acidaemias on low protein enteral feeds and to be used as a supplement with an enteral feeding protein source. Methodology All non-protein individual feed ingredients were replaced with one protein-free composite feed supplying fat, carbohydrate, and micronutrients. Thirteen subjects, median age 7.4y (3–15.5y), all nutritionally tube dependent (supplying nutritional intake:≥90%, n=12; 75%, n=1), and diagnosed with organic acidaemias (Propionic acidaemia, n=6; Vitamin B12 non-responsive methyl malonic acidaemia, n=4; Isovaleric acidaemia, n=2; Glutaric aciduria type1, n=1); were studied. Nutritional intake, biochemistry and anthropometry were monitored at week −8, 0, 12, 26 and 79. Results Energy intake remained unchanged, providing 76% of estimated energy requirements. Dietary intakes of vitamins, minerals and essential fatty acids significantly increased from week 0 to week 79, but sodium, potassium, magnesium, decosahexanoic acid and fibre did not meet suggested requirements. Plasma zinc, selenium, haemoglobin and MCV significantly improved, and growth remained satisfactory. Natural protein intake met WHO/FAO/UNU 2007 recommendations. Conclusions A protein-free composite feed formulated to meet the non-protein nutritional requirements of children aged over 1year improved nutritional intake, biochemical nutritional status, and simplified enteral tube feeding regimens in children with organic acidaemias.

      PubDate: 2017-10-07T17:47:11Z
  • The prevalence of diseases caused by lysosome-related genes in a cohort of
           undiagnosed patients

    • Authors: Filippo Pinto; Vairo Nicole Boczek Margot Cousin Charu Kaiwar Patrick
      Abstract: Publication date: December 2017
      Source:Molecular Genetics and Metabolism Reports, Volume 13
      Author(s): Filippo Pinto Vairo, Nicole J. Boczek, Margot A. Cousin, Charu Kaiwar, Patrick R. Blackburn, Erin Conboy, Brendan C. Lanpher, Ralitza H. Gavrilova, Pavel N. Pichurin, Konstantinos N. Lazaridis, Dusica Babovic-Vuksanovic, Eric W. Klee
      Lysosomal diseases (LD) comprise a group of approximately 60 hereditary conditions caused by progressive accumulation of metabolites due to defects in lysosomal enzymes and degradation pathways, which lead to a wide range of clinical manifestations. The estimated combined incidence of LD is between 1 in 4000 to 1 in 13,000 live births, with recent data from pilot newborn screening studies showing even higher incidence. We aimed to determine the prevalence of the classical LD and other diseases caused by lysosome-related genes in our cohort of diagnostic odyssey patients. The Individualized Medicine Clinic at Mayo Clinic is increasingly utilizing whole exome sequencing (WES) to determine the genetic etiology of undiagnosed Mendelian disease. From September 2012 to April 2017, WES results from 350 patients with unexplained symptoms were reviewed. Disease-causing variants were identified in MYO6, CLN6, LRBA, KCTD7, and ARSB revealing a genetic diagnosis of a LD in 8 individuals from 5 families. Based on our findings, lysosome-related disorders may be collectively common, reaching up to 1.5% prevalence in a cohort of patients with undiagnosed diseases presenting to a genetics clinic.

      PubDate: 2017-08-19T18:36:13Z
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