3,693 results match your criteria Molecular Genetics and Metabolism [Journal]


Clinical and biochemical footprints of inherited metabolic diseases. II. Metabolic liver diseases.

Mol Genet Metab 2019 Apr 12. Epub 2019 Apr 12.

Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany; Division of Metabolism, Children's Hospital, Zürich, Switzerland. Electronic address:

Inherited metabolic diseases account for about one third of pediatric patients with hepatomegaly, acute liver failure, cirrhosis or cholestasis. Specifically for pediatric acute liver failure, they account for 10-15% of cases, with a mortality of 22-65%. The percentage of acute liver failure caused by an inherited metabolic disease in children <2-3 years of age is even higher, ranging from a third to half of all cases. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.04.002DOI Listing
April 2019
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Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial.

Mol Genet Metab 2019 Apr 3. Epub 2019 Apr 3.

Department of Pediatric Metabolic Diseases, Emma Children's Hospital and Amsterdam Lysosome Center "Sphinx", Academic Medical Center, University Hospital of Amsterdam, Amsterdam, the Netherlands.

Background: Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.03.010DOI Listing
April 2019
1 Read
2.625 Impact Factor

Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs).

Mol Genet Metab 2019 Mar 6. Epub 2019 Mar 6.

Section on Gastroenterology & Hepatology, Wake Forest University School of Medicine/NC Baptist Hospital, Winston-Salem, NC 27157, United States of America.

The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192193008
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http://dx.doi.org/10.1016/j.ymgme.2019.03.002DOI Listing
March 2019
2 Reads

ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis.

Mol Genet Metab 2019 Mar 27. Epub 2019 Mar 27.

Mason Eye Institute, University of Missouri School of Medicine, Columbia, MO, USA. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs. Read More

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http://dx.doi.org/10.1016/j.ymgme.2018.11.015DOI Listing

Presence of three mutations in the fumarylacetoacetate hydrolase gene in a patient with atypical symptoms of hereditary tyrosinemia type I.

Mol Genet Metab 2019 Feb 7. Epub 2019 Feb 7.

Laboratoire de génétique cellulaire et développementale, IBIS and PROTEO, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, 1030 avenue de la Médecine, Université Laval, Québec G1V 0A6, Canada.. Electronic address:

Hereditary tyrosinemia type 1 (HT1), the most severe disease of the tyrosine catabolic pathway, is caused by a deficiency of fumarylacetoacetate hydrolase (FAH). More than 90 disease-causing variants have been identified in the fah gene. We investigated the molecular defect in a patient who presented atypical symptoms for the disease. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.019DOI Listing
February 2019
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Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook.

Mol Genet Metab 2019 Mar 27. Epub 2019 Mar 27.

Dietmar-Hopp Metabolic Center and Centre for Pediatrics and Adolescent Medicine, University Children's Hospital, Heidelberg, Germany. Electronic address:

Aromatic-l-amino acid decarboxylase (AADC) deficiency is an ultra-rare inherited autosomal recessive disorder characterized by sharply reduced synthesis of dopamine as well as other neurotransmitters. Symptoms, including hypotonia and movement disorders (especially oculogyric crisis and dystonia) as well as autonomic dysfunction and behavioral disorders, vary extensively and typically emerge in the first months of life. However, diagnosis is difficult, requiring analysis of metabolites in cerebrospinal fluid, assessment of plasma AADC activity, and/or DNA sequence analysis, and is frequently delayed for years. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.03.009DOI Listing
March 2019
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Clinical and biochemical footprints of inherited metabolic diseases. I. Movement disorders.

Mol Genet Metab 2019 Mar 26. Epub 2019 Mar 26.

Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany; Division of Metabolism, Children's Hospital, Zürich, Switzerland. Electronic address:

About a third of patients with inherited metabolic diseases with neurologic involvement suffer from a movement disorder, in the form of ataxia, hyperkinetic movements, or hypokinetic-rigid syndrome. We reviewed and updated the list of known metabolic etiologies associated with various types of movement disorders, and found approximately 200 relevant inborn errors of metabolism. This represents the first of a series of articles attempting to create and maintain a comprehensive list of clinical and metabolic differential diagnoses according to system involvement. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183073
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http://dx.doi.org/10.1016/j.ymgme.2019.03.007DOI Listing
March 2019
5 Reads

Direct-infusion based metabolomics unveils biochemical profiles of inborn errors of metabolism in cerebrospinal fluid.

Mol Genet Metab 2019 Mar 15. Epub 2019 Mar 15.

Section Metabolic Diagnostics, Department of Biomedical Genetics, Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht University, Lundlaan 6, 3584 EA Utrecht, The Netherlands. Electronic address:

Background: For inborn errors of metabolism (IEM), metabolomics is performed for three main purposes: 1) development of next generation metabolic screening platforms, 2) identification of new biomarkers in predefined patient cohorts and 3) for identification of new IEM. To date, plasma, urine and dried blood spots are used. We anticipate that cerebrospinal fluid (CSF) holds additional - valuable - information, especially for IEM with neurological involvement. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.03.005DOI Listing
March 2019
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Phase I clinical evaluation of CNSA-001 (sepiapterin), a novel pharmacological treatment for phenylketonuria and tetrahydrobiopterin deficiencies, in healthy volunteers.

Mol Genet Metab 2019 Feb 10. Epub 2019 Feb 10.

Dietmar-Hopp-Metabolic Center, University Children's Hospital, Heidelberg, Germany; Division of Metabolism, University Children's Hospital, Zurich, Switzerland. Electronic address:

Tetrahydrobiopterin (BH) is the natural cofactor of aromatic amino acid hydroxylases and essential for degradation of phenylalanine and synthesis of catecholamines and serotonin. It can be synthesized either de novo from GTP or through the salvage pathway from sepiapterin. Sepiapterin, a natural precursor of BH, is a more stable molecule and is transported more efficiently across cellular membranes, thus having potentially significant advantage over BH as a pharmacological agent for diseases associated with BH-deficient conditions. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.02.001DOI Listing
February 2019
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The prevalence of GALM mutations that cause galactosemia: A database of functionally evaluated variants.

Mol Genet Metab 2019 Mar 18. Epub 2019 Mar 18.

Department of Pediatrics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan; Tohoku Medical Megabank Organization, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan. Electronic address:

Galactosemia is a metabolic disorder that affects the appropriate metabolism of β-D-galactose. Deficiencies in three of the enzymes of the Leloir pathway, namely, GALT, GALK1, or GALE, are characterized as type I, II, and III galactosemia, respectively. Recently, we reported a novel type of galactosemia (type IV galactosemia) due to biallelic GALM mutations. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.018DOI Listing

Bardet-Biedl syndrome obesity: BBS4 regulates cellular ER stress in early adipogenesis.

Mol Genet Metab 2019 Mar 15. Epub 2019 Mar 15.

Department of Nutrition, Faculty of Health Sciences, Ariel University, 40700, Israel. Electronic address:

Background: Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy, presenting with early obesity onset. The etiology of BBS obesity involves both central and peripheral defects, through mechanisms mostly yet to be deciphered. We previously showed BBS4 expression in adipogenesis, peaking at day 3 of differentiation. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.03.006DOI Listing

Dysregulated DNA methylation of GLA gene was associated with dysfunction of autophagy.

Mol Genet Metab 2019 Mar 7. Epub 2019 Mar 7.

Advanced Clinical Research Center, Institute for Neurological Disorders, Kawasaki, Japan. Electronic address:

Lysosomes are an essential organ for cellular metabolism and play an important role in autophagy. We examined the association between methylation and autophagy in a severely affected female patient with Fabry disease, which is caused by mutation of the GLA gene on the X chromosome, and her two sisters, who had few symptoms. We confirmed autophagic flux by LC3 turnover assay using fibroblasts from each sister. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.03.003DOI Listing
March 2019
6 Reads

Evaluation of age of death in Niemann-Pick disease, type C: Utility of disease support group websites to understand natural history.

Mol Genet Metab 2019 Feb 15. Epub 2019 Feb 15.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD, USA. Electronic address:

Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disease affecting the visceral organs and the central nervous system. The age of initial presentation varies from fetal to adult onset, although childhood onset is most common. The life expectancy for the full spectrum of NPC patients is not well defined, and it is unknown if current supportive care impacts the natural history. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.02.004DOI Listing
February 2019
4 Reads

Glycemic control and complications in glycogen storage disease type I: Results from the Swiss registry.

Mol Genet Metab 2019 Feb 28. Epub 2019 Feb 28.

Department of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland; radiz - Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, Switzerland. Electronic address:

Background: Regular carbohydrate intake to avoid hypoglycemia is the mainstay of dietary treatment in glycogen storage disease type I (GSDI). The aim of this study was to evaluate the quality of dietary treatment and glycemic control in a cohort of GSDI patients, in relation to the presence of typical long-term complications.

Methods: Data of 25 patients (22 GSD subtype Ia and 3 GSDIb, median age 20y) from the Swiss hepatic glycogen storage disease registry was analyzed cross-sectionally. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192193003
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http://dx.doi.org/10.1016/j.ymgme.2019.02.008DOI Listing
February 2019
12 Reads

Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment.

Mol Genet Metab 2019 Feb 25. Epub 2019 Feb 25.

Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address:

Background And Aim: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.02.003DOI Listing
February 2019
3 Reads

Spontaneous MRI improvement and absence of cerebral calcification in Aicardi-Goutières syndrome: Diagnostic and disease-monitoring implications.

Mol Genet Metab 2019 Feb 25. Epub 2019 Feb 25.

Department of Pediatric Radiology and Neuroradiology, V. Buzzi Children's Hospital, Milan, Italy.

Background: Aicardi-Goutières syndrome (AGS) is a rare genetic leukoencephalopathy related to inappropriate activation of type I interferon. Neuroradiological findings are typically characterized by white matter abnormalities, cerebral atrophy and cerebral calcification. The disease usually manifests itself during the first year of life in the form of an initial "encephalitic-like" phase followed by a chronic phase of stabilization of the neurological signs. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.02.006DOI Listing
February 2019
2 Reads

Genetic deletion of soluble 5'-nucleotidase II reduces body weight gain and insulin resistance induced by a high-fat diet.

Mol Genet Metab 2019 Feb 14. Epub 2019 Feb 14.

Université catholique de Louvain and de Duve Institute, Avenue Hippocrate 75, B-1200 Brussels, Belgium. Electronic address:

We previously investigated whether inhibition of AMP-metabolizing enzymes could enhance AMP-activated protein kinase (AMPK) activation in skeletal muscle for the treatment of type 2 diabetes. Soluble 5'-nucleotidase II (NT5C2) hydrolyzes IMP and its inhibition could potentially lead to a rise in AMP to activate AMPK. In the present study, we investigated effects of NT5C2 deletion in mice fed a normal-chow diet (NCD) or a high-fat diet (HFD). Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.017DOI Listing
February 2019
2 Reads

Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: Post-marketing surveillance in Japan.

Mol Genet Metab 2019 Feb 20. Epub 2019 Feb 20.

Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.

Fabry disease is a rare X-linked inherited multisystem disorder resulting from deficiency of the lysosomal enzyme alpha-galactosidase A. Currently, specific therapies, including enzyme replacement therapies, are available for Fabry disease, but clinical trials provide limited information on long-term safety and effectiveness. Agalsidase alfa was approved in Japan in 2006. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.02.005DOI Listing
February 2019
3 Reads

Recognition of alpha-mannosidosis in paediatric and adult patients: Presentation of a diagnostic algorithm from an international working group.

Mol Genet Metab 2019 Jan 31. Epub 2019 Jan 31.

University Medical Center Mainz, Dept. of Pediatric and Adolescent Medicine, Mainz, Germany.

Alpha-mannosidosis is an ultra-rare progressive lysosomal storage disorder caused by deficiency of alpha-mannosidase. Timely diagnosis of the disease has the potential to influence patient outcomes as preventive therapies can be initiated at an early stage. However, no internationally-recognised algorithm is currently available for the diagnosis of the disease. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.024DOI Listing
January 2019
2 Reads

Characterization of the hepatic transcriptome following phenobarbital induction in mice with AIP.

Mol Genet Metab 2019 Jan 6. Epub 2019 Jan 6.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Acute Intermittent Porphyria (AIP), an autosomal dominant hepatic disorder, results from hydroxymethylbilane synthase (HMBS) mutations that decrease the encoded enzymatic activity, thereby predisposing patients to life-threatening acute neurovisceral attacks. The ~1% penetrance of AIP suggests that other genetic factors modulate the onset and severity of the acute attacks. Here, we characterized the hepatic transcriptomic response to phenobarbital (PB) administration in AIP mice, which mimics the biochemical attacks of AIP. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183048
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http://dx.doi.org/10.1016/j.ymgme.2018.12.010DOI Listing
January 2019
4 Reads

Regulation and tissue-specific expression of δ-aminolevulinic acid synthases in non-syndromic sideroblastic anemias and porphyrias.

Mol Genet Metab 2019 Jan 23. Epub 2019 Jan 23.

INSERM U1149, CNRS ERL 8252, Centre de Recherche sur l'inflammation, Université Paris Diderot, site Bichat, Sorbonne Paris Cité, France, 16 rue Henri Huchard, 75018 Paris, France; Laboratory of Excellence, GR-Ex, Paris, France; AP-HP, HUPNVS, Centre Français des Porphyries, Hôpital Louis Mourier, Colombes, France. Electronic address:

Recently, new genes and molecular mechanisms have been identified in patients with porphyrias and sideroblastic anemias (SA). They all modulate either directly or indirectly the δ-aminolevulinic acid synthase (ALAS) activity. ALAS, is encoded by two genes: the erythroid-specific (ALAS2), and the ubiquitously expressed (ALAS1). Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.015DOI Listing
January 2019
4 Reads

Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies.

Mol Genet Metab 2019 Jan 18. Epub 2019 Jan 18.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Mouse models of the human porphyrias have proven useful for investigations of disease pathogenesis and to facilitate the development of new therapeutic approaches. To date, mouse models have been generated for all major porphyrias, with the exception of X-linked protoporphyria (XLP) and the ultra rare 5-aminolevulinic acid dehydratase deficient porphyria (ADP). Mouse models have been generated for the three autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.007DOI Listing
January 2019
6 Reads

The ability of an LC-MS/MS-based erythrocyte GALT enzyme assay to predict the phenotype in subjects with GALT deficiency.

Mol Genet Metab 2019 Jan 22. Epub 2019 Jan 22.

Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States. Electronic address:

Background: GALT deficiency is a rare genetic disorder of carbohydrate metabolism. Due to the decreased activity or absence of the enzyme galactose-1-phosphate uridylyltransferase (GALT), cells from affected individuals are unable to metabolize galactose normally. Lactose consumption in the newborn period could potentially lead to a lethal disease process with multi-organ involvement. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.016DOI Listing
January 2019
4 Reads

Psychosocial issues in erythropoietic protoporphyria - the perspective of parents, children, and young adults: A qualitative study.

Mol Genet Metab 2019 Jan 26. Epub 2019 Jan 26.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address:

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare photodermatoses, generally presenting in childhood with severe and painful phototoxicity. EPP has been reported to negatively affect quality of life (QoL), but there is limited information on the psychosocial issues faced by patients and families. To address this, an online focus group study was conducted to explore the perspective of parents of children with EPP, and young adults and children with EPP. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.023DOI Listing
January 2019
2 Reads

Mild inborn errors of metabolism in commonly used inbred mouse strains.

Mol Genet Metab 2019 Jan 24. Epub 2019 Jan 24.

Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA. Electronic address:

Inbred mouse strains are a cornerstone of translational research but paradoxically many strains carry mild inborn errors of metabolism. For example, α-aminoadipic acidemia and branched-chain ketoacid dehydrogenase deficiency are known in C57BL/6J mice. Using RNA sequencing, we now reveal the causal variants in Dhtkd1 and Bckdhb, and the molecular mechanism underlying these metabolic defects. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183071
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http://dx.doi.org/10.1016/j.ymgme.2019.01.021DOI Listing
January 2019
10 Reads
2.625 Impact Factor

The mitochondrial heme metabolon: Insights into the complex(ity) of heme synthesis and distribution.

Mol Genet Metab 2019 Jan 17. Epub 2019 Jan 17.

Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, United States; Biomedical and Health Sciences Institute, University of Georgia, Athens, GA 30602, United States; Augusta University-University of Georgia, Medical Partnership, Athens, GA 30602, United States. Electronic address:

Heme is an essential cofactor in metazoans that is also toxic in its free state. Heme is synthesized by most metazoans and must be delivered to all cellular compartments for incorporation into a variety of hemoproteins. The heme biosynthesis enzymes have been proposed to exist in a metabolon, a protein complex consisting of interacting enzymes in a metabolic pathway. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.006DOI Listing
January 2019
2 Reads

The nuclear background influences the penetrance of the near-homoplasmic m.1630 A > G MELAS variant in a symptomatic proband and asymptomatic mother.

Mol Genet Metab 2019 Jan 25. Epub 2019 Jan 25.

Department of Anatomy and Cell Biology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA. Electronic address:

In this study, we report the metabolic consequences of the m.1630 A > G variant in fibroblasts from the symptomatic proband affected with the mitochondrial encephalomyopathy lactic acidosis and stroke-like episode Syndrome and her asymptomatic mother. By long-range PCR followed by massively parallel sequencing of the mitochondrial genome, we accurately measured heteroplasmy in fibroblasts from the proband (89. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.022DOI Listing
January 2019
9 Reads

Erythropoietic Protoporphyria and X-Linked Protoporphyria: pathophysiology, genetics, clinical manifestations, and management.

Authors:
Manisha Balwani

Mol Genet Metab 2019 Jan 24. Epub 2019 Jan 24.

Department of Genetics and Genomic Sciences and Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States. Electronic address:

Erythropoietic Protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare, genetic photodermatoses resulting from defects in enzymes of the heme-biosynthetic pathway. EPP results from the partial deficiency of ferrochelatase, and XLP results from gain-of-function mutations in erythroid specific ALAS2. Both disorders result in the accumulation of erythrocyte protoporphyrin, which is released in the plasma and taken up by the liver and vascular endothelium. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183064
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http://dx.doi.org/10.1016/j.ymgme.2019.01.020DOI Listing
January 2019
5 Reads

Recessive GM3 synthase deficiency: Natural history, biochemistry, and therapeutic frontier.

Mol Genet Metab 2019 Jan 21. Epub 2019 Jan 21.

Clinic for Special Children, Strasburg, PA, USA. Electronic address:

GM3 synthase, encoded by ST3GAL5, initiates synthesis of all downstream cerebral gangliosides. Here, we present biochemical, functional, and natural history data from 50 individuals homozygous for a pathogenic ST3GAL5 c.862C>T founder allele (median age 8. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.013DOI Listing
January 2019
14 Reads

Trps1 transcription factor regulates mineralization of dental tissues and proliferation of tooth organ cells.

Mol Genet Metab 2019 Jan 23. Epub 2019 Jan 23.

Center for Craniofacial Regeneration, Dept. of Oral Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA. Electronic address:

Mutations of the TRPS1 gene cause trichorhinophalangeal syndrome (TRPS), a skeletal dysplasia with dental abnormalities. TRPS dental phenotypes suggest that TRPS1 regulates multiple aspects of odontogenesis, including the tooth number and size. Previous studies delineating Trps1 expression throughout embryonic tooth development in mice detected strong Trps1 expression in dental mesenchyme, preodontoblasts, and dental follicles, suggesting that TRPS dental phenotypes result from abnormalities in early developmental processes. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.014DOI Listing
January 2019
2 Reads

Ammonium accumulation and chemokine decrease in culture media of Gcdh 3D reaggregated brain cell cultures.

Mol Genet Metab 2019 Jan 18. Epub 2019 Jan 18.

Pediatric Metabolic Disease Unit, Department of Pediatrics, Lausanne University Hospital, Chemin de Mont-Paisible 18, 1011 Lausanne, Switzerland. Electronic address:

Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.009DOI Listing
January 2019
3 Reads

Congenital erythropoietic porphyria: Recent advances.

Mol Genet Metab 2018 Dec 27. Epub 2018 Dec 27.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America. Electronic address:

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by photosensitivity and by hematologic abnormalities in affected individuals. CEP is caused by mutations in the uroporphyrinogen synthase (UROS) gene. In three reported cases, CEP has been associated with a specific X-linked GATA1 mutation. Read More

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http://dx.doi.org/10.1016/j.ymgme.2018.12.008DOI Listing
December 2018
14 Reads

Swallowing dysfunction in patients with nephropathic cystinosis.

Mol Genet Metab 2019 Jan 22. Epub 2019 Jan 22.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Introduction: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.011DOI Listing
January 2019
4 Reads

Porphyria cutanea tarda: Recent update.

Authors:
Ashwani K Singal

Mol Genet Metab 2019 Jan 18. Epub 2019 Jan 18.

Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address:

Porphyria cutanea tarda (PCT) is the most common human porphyria, due to hepatic deficiency of uroporphyrinogen decarboxylase (UROD), which is acquired in the presence of iron overload and various susceptibility factors, such as alcohol abuse, smoking, hepatitis C virus (HCV) infection, HIV infection, iron overload with HFE gene mutations, use of estrogens, and UROD mutation. Patients with familial or type II PCT due to autosomal dominant UROD mutation also require other susceptibility factors, as the disease phenotype requires hepatic UROD deficiency to below 20% of normal. PCT clinically manifests with increased skin fragility and blistering skin lesions on sun exposed areas. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183057
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http://dx.doi.org/10.1016/j.ymgme.2019.01.004DOI Listing
January 2019
9 Reads

Ketogenic and anaplerotic dietary modifications ameliorate seizure activity in Drosophila models of mitochondrial encephalomyopathy and glycolytic enzymopathy.

Mol Genet Metab 2019 Jan 17. Epub 2019 Jan 17.

Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Pittsburgh Institute for Neurodegenerative Diseases (PIND), University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Seizures are a feature not only of the many forms of epilepsy, but also of global metabolic diseases such as mitochondrial encephalomyopathy (ME) and glycolytic enzymopathy (GE). Modern anti-epileptic drugs (AEDs) are successful in many cases, but some patients are refractory to existing AEDs, which has led to a surge in interest in clinically managed dietary therapy such as the ketogenic diet (KD). This high-fat, low-carbohydrate diet causes a cellular switch from glycolysis to fatty acid oxidation and ketone body generation, with a wide array of downstream effects at the genetic, protein, and metabolite level that may mediate seizure protection. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.008DOI Listing
January 2019
2 Reads

GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia.

Mol Genet Metab 2019 Jan 7. Epub 2019 Jan 7.

INSERM U1149, Centre de Recherche sur l'inflammation (CRI), Paris, France; Université Paris Diderot, site Bichat, Sorbonne Paris cité, DHU UNITY, Paris, France; Laboratory of excellence GR-Ex, Paris, France. Electronic address:

Non-syndromic microcytic congenital sideroblastic anemia (cSA) is predominantly caused by defective genes encoding for either ALAS2, the first enzyme of heme biosynthesis pathway or SLC25A38, the mitochondrial importer of glycine, an ALAS2 substrate. Herein we explored a new case of cSA with two mutations in GLRX5, a gene for which only two patients have been reported so far. The patient was a young female with biallelic compound heterozygous mutations in GLRX5 (p. Read More

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http://dx.doi.org/10.1016/j.ymgme.2018.12.012DOI Listing
January 2019
6 Reads
2.625 Impact Factor

WORLDSymposium™ 2019 Program.

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Mol Genet Metab 2019 Feb 29;126(2):S7-S16. Epub 2018 Dec 29.

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http://dx.doi.org/10.1016/j.ymgme.2018.12.015DOI Listing
February 2019
2 Reads

WORLDSymposium™ 2019 Introduction.

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Mol Genet Metab 2019 Feb 31;126(2):S2-S6. Epub 2018 Dec 31.

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http://dx.doi.org/10.1016/j.ymgme.2018.12.014DOI Listing
February 2019
2 Reads

Early-onset of symptoms and clinical course of Pompe disease associated with the c.-32-13 T > G variant.

Mol Genet Metab 2019 Feb 23;126(2):106-116. Epub 2018 Aug 23.

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 905 S. LaSalle street, GSRB1, Durham, NC, USA. Electronic address:

Background: Individuals with late-onset Pompe disease (LOPD) and the common c.-32-13 T > G variant are widely thought to have milder, adult-onset disease. This belief, and the consequent low suspicion of clinical involvement in children, has led to delays in diagnosis and treatment initiation in patients with early onset of symptoms. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183028
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http://dx.doi.org/10.1016/j.ymgme.2018.08.009DOI Listing
February 2019
18 Reads

Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood.

Mol Genet Metab 2019 Mar 5;126(3):250-258. Epub 2019 Jan 5.

Department of Child Neurology, Hospital Vall d'Hebron - Institut de Recerca (VHIR), Barcelona, Spain; CIBERER, Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain; Faculty of Medicine, Universitat Autónoma de Barcelona, Unitat Docent Vall d'Hebrón, Spain. Electronic address:

Aim: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations.

Method: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts.

Results: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183069
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http://dx.doi.org/10.1016/j.ymgme.2019.01.001DOI Listing
March 2019
11 Reads

Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria.

Mol Genet Metab 2019 Jan 7. Epub 2019 Jan 7.

Section on Gastroenterology & Hepatology, Wake Forest University/NC Baptist Medical Center, Winston-Salem, NC, USA. Electronic address:

Background And Aims: Acute intermittent porphyria (AIP) results from a partial deficiency of porphobilinogen deaminase (PBGD). Symptomatic AIP patients, most of whom are women, experience acute attacks characterized by severe abdominal pain and abrupt increases in blood pressure. Here, we characterized the reactivity of mesenteric arteries from male and female AIP mice with ~30% of normal PBGD activity and wild type C57BL/6 mice. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183058
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http://dx.doi.org/10.1016/j.ymgme.2019.01.005DOI Listing
January 2019
4 Reads

Identification of nucleolar protein NOM1 as a novel nuclear IGF1R-interacting protein.

Mol Genet Metab 2019 Mar 4;126(3):259-265. Epub 2019 Jan 4.

Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Yoran Institute for Human Genome Research, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address:

The insulin-like growth factor-1 receptor (IGF1R) mediates the biological actions of both IGF1 and IGF2. In recent years, evidence has accumulated showing that, in addition to its classical cell-surface distribution, IGF1R translocates to cell nucleus via an apparently SUMO-1-dependent mechanism. While the role of IGF1R in nucleus has not yet been settled, available information suggests that the nuclear receptor displays activities usually linked to transcription factors, including DNA binding and transcription regulation. Read More

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http://dx.doi.org/10.1016/j.ymgme.2019.01.002DOI Listing
March 2019
2 Reads

Computational disease model of phenobarbital-induced acute attacks in an acute intermittent porphyria mouse model.

Mol Genet Metab 2018 Dec 21. Epub 2018 Dec 21.

Pharmacometrics & Systems Pharmacology Research Unit, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.

Introduction: Acute intermittent porphyria (AIP) is characterized by hepatic over-production of the heme precursors when aminolevulinic acid (ALA)-synthase 1 is induced by endogenous or environmental factors. The aim of this study was to develop a semi-mechanistic computational model to characterize urine accumulation of heme precursors during acute attacks based on experimental pharmacodynamics data and support the development of new therapeutic strategies.

Methods: Male AIP mice received recurrent phenobarbital challenge starting on days 1, 9, 16 and 30. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183057
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http://dx.doi.org/10.1016/j.ymgme.2018.12.009DOI Listing
December 2018
15 Reads

Program and Abstracts WORLDSymposium 2019* 15th Annual Research Meeting.

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Mol Genet Metab 2019 Feb 29;126(2):S1. Epub 2018 Dec 29.

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http://dx.doi.org/10.1016/j.ymgme.2018.12.013DOI Listing
February 2019
2 Reads

Final results of the phase 1/2, open-label clinical study of intravenous recombinant human N-acetyl-α-d-glucosaminidase (SBC-103) in children with mucopolysaccharidosis IIIB.

Mol Genet Metab 2019 Feb 6;126(2):131-138. Epub 2018 Dec 6.

Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Electronic address:

Mucopolysaccharidosis IIIB is caused by a marked decrease in N-acetyl-α-d-glucosaminidase (NAGLU) enzyme activity, which leads to the accumulation of heparan sulfate in key organs, progressive brain atrophy, and neurocognitive decline. In this open-label study, 11 eligible patients aged 2 to <12 years (developmental age ≥ 1 year) were sequentially allocated to recombinant human NAGLU enzyme (SBC-103) in 3 staggered- and escalating-dose groups (0.3 mg/kg [n = 3], 1. Read More

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http://dx.doi.org/10.1016/j.ymgme.2018.12.003DOI Listing
February 2019
6 Reads

Zebrafish as a model system to delineate the role of heme and iron metabolism during erythropoiesis.

Mol Genet Metab 2018 Dec 24. Epub 2018 Dec 24.

Department of Animal & Avian Sciences and Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742, USA. Electronic address:

Coordination of iron acquisition and heme synthesis is required for effective erythropoiesis. The small teleost zebrafish (Danio rerio) is an ideal vertebrate animal model to replicate various aspects of human physiology and provides an efficient and cost-effective way to model human pathophysiology. Importantly, zebrafish erythropoiesis largely resembles mammalian erythropoiesis. Read More

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http://dx.doi.org/10.1016/j.ymgme.2018.12.007DOI Listing
December 2018
3 Reads

RNA-Seq analysis in an avian model of maternal phenylketonuria.

Mol Genet Metab 2019 Jan 6;126(1):23-29. Epub 2018 Sep 6.

Department of Biology, University of Central Oklahoma, Edmond, OK, USA. Electronic address:

Cardiac malformations (CVMs) are a leading cause of infant morbidity and mortality. CVMs are particularly prevalent when the developing fetus is exposed to high levels of phenylalanine in-utero in mothers with Phenylketonuria. Yet, elucidating the underlying molecular mechanism leading to CVMs has proven difficult. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183025
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http://dx.doi.org/10.1016/j.ymgme.2018.09.003DOI Listing
January 2019
7 Reads

Neurocognitive functioning in adults with phenylketonuria: Report of a 10-year follow-up.

Mol Genet Metab 2019 Mar 26;126(3):246-249. Epub 2018 Dec 26.

University of Münster, Department of Pediatrics, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.

Background: The long-term prognosis of early treated phenylketonuria (PKU) is still under discussion. Aim of this controlled long-term study was to assess the neurological and neuropsychological outcome in adult patients with early-treated PKU.

Methods: We investigated 35 patients with early-treated classical PKU aged 29 to 51 years (mean age 41 years) and 18 healthy controls matched for age and socioeconomic status. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10967192183060
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http://dx.doi.org/10.1016/j.ymgme.2018.12.011DOI Listing
March 2019
10 Reads

Early detection of organ involvement in Fabry disease by biomarker assessment in conjunction with LGE cardiac MRI: results from the SOPHIA study.

Mol Genet Metab 2019 Feb 12;126(2):169-182. Epub 2018 Nov 12.

Zentrum für Kinder- und Jugendmedizin der Universitätsmedizin Mainz, Mainz, Germany. Electronic address:

Background: Initiation of enzyme replacement therapy (ERT) early in the Fabry disease course may facilitate better outcomes than in patients with advanced disease. Early diagnosis is often hindered by the heterogeneous nature of signs and symptoms, and by the presentation of atypical phenotypes.

Methods: The Sophisticated Assessment of Disease Burden in Patients with Fabry Disease study (SOPHIA; ClinicalTrials. Read More

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http://dx.doi.org/10.1016/j.ymgme.2018.11.005DOI Listing
February 2019
4 Reads