5,040 results match your criteria Journal of Inherited Metabolic Disease [Journal]


AAV9 Gene Replacement Therapy for Respiratory Insufficiency in Very-long Chain Acyl-CoA Dehydrogenase Deficiency.

J Inherit Metab Dis 2019 Apr 17. Epub 2019 Apr 17.

Department of Pediatrics, Duke University, Durham, NC.

Very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is an autosomal recessive disorder of fatty acid oxidation. Fatty acids are a major source of energy during catabolic stress, so the abscense of VLCAD can result in a metabolic crises and respiratory insufficiency. The etiology of this respiratory insufficiency is unclear. Read More

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http://dx.doi.org/10.1002/jimd.12101DOI Listing

Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision.

J Inherit Metab Dis 2019 Apr 14. Epub 2019 Apr 14.

Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.

In 2012 we published guidelines summarizing and evaluating late 2011 evidence for diagnosis and therapy of urea cycle disorders (UCDs). With 1:35,000 estimated incidence, UCDs cause hyperammonemia of neonatal (~50%) or late onset that can lead to intellectual disability or death, even while effective therapies do exist. In the 7 years that have elapsed since the first guideline was published, abundant novel information has accumulated, experience on newborn screening for some UCDs has widened, a novel hyperammonemia-causing genetic disorder has been reported, glycerol phenylbutyrate has been introduced as a treatment, and novel promising therapeutic avenues (including gene therapy) have been opened. Read More

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http://dx.doi.org/10.1002/jimd.12100DOI Listing
April 2019
2 Reads

Natural History, with Clinical, Biochemical and Molecular Characterization, of Classical Homocystinuria in the Qatari Population.

J Inherit Metab Dis 2019 Apr 10. Epub 2019 Apr 10.

Clinical and Metabolic Genetics, Department of Pediatrics, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.

Background: Classical homocystinuria (HCU) is the most common inborn error of metabolism in Qatar, with an incidence of 1:1800, and is caused by the Qatari founder p.R336C mutation in the CBS gene. This study describes the natural history and clinical manifestations of HCU in the Qatari population. Read More

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http://dx.doi.org/10.1002/jimd.12099DOI Listing
April 2019
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Implementation of a Fast Method for the Measurement of Carnitine Palmitoyltransferase 2 (CPT2) Activity in Lymphocytes by Tandem Mass Spectrometry as Confirmation for Newborn Screening.

J Inherit Metab Dis 2019 Apr 8. Epub 2019 Apr 8.

Department of General Pediatrics, Center for Pediatrics and Adolescent Medicine, Medical Centre- University of Freiburg, Faculty of Medicine, Freiburg, Germany.

Carnitine palmitoyltransferase II (CPT2) is a rare autosomal recessive inherited disorder affecting mitochondrial β-oxidation. Confirmation diagnostics are mostly based on molecular sequencing of the CPT2 gene, especially to distinguish CPT2 and carnitine aclycarnitine translocase (CACT) deficiencies, which present with identical acylcarnitine profiles on newborn screening. In the past different enzyme tests in muscle biopsies have been developed in order to study the functional effect in one of the main target organs. Read More

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http://dx.doi.org/10.1002/jimd.12098DOI Listing
April 2019
2 Reads
3.365 Impact Factor

Mutations in the translocon-associated protein complex subunit SSR3 cause a novel congenital disorder of glycosylation.

J Inherit Metab Dis 2019 Apr 3. Epub 2019 Apr 3.

Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

The translocon-associated protein (TRAP) complex facilitates the translocation of proteins across the endoplasmic reticulum membrane and associates with the oligosaccharyl transferase (OST) complex to maintain proper glycosylation of nascent polypeptides. Pathogenic variants in either complex cause a group of rare genetic disorders termed, congenital disorders of glycosylation (CDG). We report an individual who presented with severe intellectual and developmental disabilities and sensorineural deafness with an unsolved type I CDG, and sought to identify the underlying genetic basis. Read More

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http://dx.doi.org/10.1002/jimd.12091DOI Listing
April 2019
1 Read
3.365 Impact Factor

Bone development and remodeling in metabolic disorders.

J Inherit Metab Dis 2019 Apr 3. Epub 2019 Apr 3.

Department of Genetics, Microbiology and Statistics, Faculty of Biology, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain.

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http://dx.doi.org/10.1002/jimd.12097DOI Listing

Challenges in diagnosing and managing adult patients with Urea Cycle Disorders.

J Inherit Metab Dis 2019 Apr 1. Epub 2019 Apr 1.

National Centre for Inherited Metabolic Diseases, The Mater Misericordiae University Hospital, Dublin 7, Ireland.

Urea cycle disorders (UCD) are a group of rare inherited metabolic conditions of amino acid catabolism caused by an enzyme deficiency within the hepatic ammonia detoxification pathway. The presentation of these disorders ranges from life-threatening intoxication in the neonate to asymptomatic status in adults. Late-onset UCDs can present for the first time in adulthood and may mimic other causes of acute confusion or psychiatric diseases, and are often associated with neurological symptoms. Read More

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http://dx.doi.org/10.1002/jimd.12096DOI Listing
April 2019
3 Reads

Towards understanding tissue-specific symptoms in dolichol-phosphate-mannose synthesis disorders; insight from DPM3-CDG.

J Inherit Metab Dis 2019 Mar 31. Epub 2019 Mar 31.

Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.

The Congenital Disorders of Glycosylation (CDG) are inborn errors of metabolism with a great genetic heterogeneity. Most CDG are caused by defects in the N-glycan biosynthesis, leading to multisystem phenotypes. However, the occurrence of tissue-restricted clinical symptoms in the various defects in dolichol-phosphate-mannose (DPM) synthesis remains unexplained. Read More

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http://dx.doi.org/10.1002/jimd.12095DOI Listing

Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome.

J Inherit Metab Dis 2019 Mar 29. Epub 2019 Mar 29.

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.

Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6'6'H2 glucose and U- C palmitate and indirect calorimetry during rest, 30-minutes of moderate exercise (50% ), and recovery. Read More

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http://dx.doi.org/10.1002/jimd.12094DOI Listing

Cerebral folate deficiency: Analytical tests and differential diagnosis.

J Inherit Metab Dis 2019 Mar 27. Epub 2019 Mar 27.

Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK.

Cerebral folate deficiency is typically defined as a deficiency of the major folate species 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) in the presence of normal peripheral total folate levels. However, it should be noted that cerebral folate deficiency is also often used to describe conditions where CSF 5-MTHF is low, in the presence of low or undefined peripheral folate levels. Known defects of folate transport are deficiency of the proton coupled folate transporter, associated with systemic as well as cerebral folate deficiency, and deficiency of the folate receptor alpha, leading to an isolated cerebral folate deficiency associated with intractable seizures, developmental delay and/or regression, progressive ataxia and choreoathetoid movement disorders. Read More

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http://dx.doi.org/10.1002/jimd.12092DOI Listing
March 2019
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Exploiting epigenetics for the treatment of inborn errors of metabolism.

J Inherit Metab Dis 2019 Mar 27. Epub 2019 Mar 27.

Departments of Pediatrics, University of Groningen, University Medical Center Groningen, GZ, Groningen, The Netherlands.

Gene therapy is currently considered as the optimal treatment for Inborn Errors of Metabolism (IEMs), as it aims to permanently compensate for the primary genetic defect. However, emerging gene editing approaches such as CRISPR-Cas9, in which the DNA of the host organism is edited at a precise location, may have outperforming therapeutic potential. Gene editing strategies aim to correct the actual genetic mutation, while circumventing issues associated with conventional compensation gene therapy. Read More

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http://dx.doi.org/10.1002/jimd.12093DOI Listing
March 2019
3 Reads

Argininosuccinate neurotoxicity and prevention by creatine in argininosuccinate lyase deficiency: An in vitro study in rat three-dimensional organotypic brain cell cultures.

J Inherit Metab Dis 2019 Mar 25. Epub 2019 Mar 25.

Service of Clinical Chemistry, Lausanne University Hospital and University of Lausanne, Switzerland.

The urea cycle disorder (UCD) argininosuccinate lyase (ASL) deficiency, caused by a defective ASL enzyme, exhibits a wide range of phenotypes, from life-threatening neonatal hyperammonemia to asymptomatic patients, with only the biochemical marker argininosuccinic acid (ASA) elevated in body fluids. Remarkably, even without ever suffering from hyperammonemia, patients often develop severe cognitive impairment and seizures. The goal of this study was to understand the effect on the known toxic metabolite ASA and the assumed toxic metabolite guanidinosuccinic acid (GSA) on developing brain cells, and to evaluate the potential role of creatine (Cr) supplementation, as it was described protective for brain cells exposed to ammonia. Read More

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http://dx.doi.org/10.1002/jimd.12090DOI Listing
March 2019
1 Read

Desmosterolosis and desmosterol homeostasis in the developing mouse brain.

J Inherit Metab Dis 2019 Mar 19. Epub 2019 Mar 19.

Department of Pediatrics, Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska.

Cholesterol serves as a building material for cellular membranes and plays an important role in cellular metabolism. The brain relies on its own cholesterol biosynthesis, which starts during embryonic development. Cholesterol is synthesized from two immediate precursors, desmosterol and 7-dehydrocholesterol (7-DHC). Read More

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http://dx.doi.org/10.1002/jimd.12088DOI Listing
March 2019
1 Read

Phosphoglycerate kinase deficiency: A nationwide multicenter retrospective study.

J Inherit Metab Dis 2019 Mar 19. Epub 2019 Mar 19.

Neurology Department, Hôpital Raymond Poincaré, Paris, France.

Phosphoglycerate kinase (PGK) deficiency is a rare X-linked metabolic disorder caused by mutations in the PGK1 gene. Patients usually develop various combinations of nonspherocytic hemolytic anemia (NSHA), myopathy, and central nervous system disorders. In this national multicenter observational retrospective study, we recorded all known French patients with PGK deficiency, and 3 unrelated patients were identified. Read More

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http://dx.doi.org/10.1002/jimd.12087DOI Listing
March 2019
1 Read

Proposal for a simplified classification of IMD based on a pathophysiological approach: a practical guide for clinicians.

J Inherit Metab Dis 2019 Mar 18. Epub 2019 Mar 18.

Neurology Department. Neurometabolic Unit and Synaptic Metabolism Lab. Institut Pediàtric de Recerca. Hospital Sant Joan de Déu, metabERN and CIBERER-ISCIII, Barcelona, Spain.

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http://dx.doi.org/10.1002/jimd.12086DOI Listing

Biomarkers of oxidative stress, inflammation, and vascular dysfunction in inherited cystathionine β-synthase deficient homocystinuria and the impact of taurine treatment in a phase 1/2 human clinical trial.

J Inherit Metab Dis 2019 Mar 14. Epub 2019 Mar 14.

Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado.

Study Objective: A phase 1/2 clinical trial was performed in individuals with cystathionine β synthase (CBS) deficient homocystinuria with aims to: (a) assess pharmacokinetics and safety of taurine therapy, (b) evaluate oxidative stress, inflammation, and vascular function in CBS deficiency, and (c) evaluate the impact of short-term taurine treatment.

Methods: Individuals with pyridoxine-nonresponsive CBS deficiency with homocysteine >50 μM, without inflammatory disorder or on antioxidant therapy were enrolled. Biomarkers of oxidative stress and inflammation, endothelial function (brachial artery flow-mediated dilation [FMD]), and disease-related metabolites obtained at baseline were compared to normal values. Read More

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http://dx.doi.org/10.1002/jimd.12085DOI Listing
March 2019
2 Reads

Organelle interplay-peroxisome interactions in health and disease.

J Inherit Metab Dis 2019 Mar 12. Epub 2019 Mar 12.

Institute of Neuroanatomy, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Manheim, University of Heidelberg, Mannheim, Germany.

Peroxisomes are multifunctional, dynamic, membrane-bound organelles with important functions in cellular lipid metabolism, rendering them essential for human health and development. Important roles for peroxisomes in signaling and the fine-tuning of cellular processes are emerging, which integrate them in a complex network of interacting cellular compartments. Like many other organelles, peroxisomes communicate through membrane contact sites. Read More

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http://dx.doi.org/10.1002/jimd.12083DOI Listing

Novel insights into the clinical and molecular spectrum of congenital disorders of autophagy.

J Inherit Metab Dis 2019 Mar 10. Epub 2019 Mar 10.

Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Autophagy is a fundamental and conserved catabolic pathway that mediates the degradation of macromolecules and organelles in lysosomes. Autophagy is particularly important to postmitotic and metabolically active cells such as neurons. The complex architecture of neurons and their long axons pose additional challenges for efficient recycling of cargo. Read More

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http://dx.doi.org/10.1002/jimd.12084DOI Listing
March 2019
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Functional disruption of pyrimidine nucleoside transporter CNT1 results in a novel inborn error of metabolism with high excretion of uridine and cytidine.

J Inherit Metab Dis 2019 Mar 7. Epub 2019 Mar 7.

Department Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboudumc, Nijmegen, The Netherlands.

Genetic defects in the pyrimidine nucleoside transporters of the CNT transporter family have not yet been reported. Metabolic investigations in a patient with infantile afebrile tonic-clonic seizures revealed increased urinary uridine and cytidine excretion. Segregation of this metabolic trait in the family showed the same biochemical phenotype in a healthy older brother of the index. Read More

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http://dx.doi.org/10.1002/jimd.12081DOI Listing

A liver-humanized mouse model of carbamoyl phosphate synthetase 1-deficiency.

J Inherit Metab Dis 2019 Mar 6. Epub 2019 Mar 6.

Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden.

A liver-humanized mouse model for CPS1-deficiency was generated by the high-level repopulation of the mouse liver with CPS1-deficient human hepatocytes. When compared with mice that are highly repopulated with CPS1-proficient human hepatocytes, mice that are repopulated with CPS1-deficient human hepatocytes exhibited characteristic symptoms of human CPS1 deficiency including an 80% reduction in CPS1 metabolic activity, delayed clearance of an ammonium chloride infusion, elevated glutamine and glutamate levels, and impaired metabolism of [ N]ammonium chloride into urea, with no other obvious phenotypic differences. Because most metabolic liver diseases result from mutations that alter critical pathways in hepatocytes, a model that incorporates actual disease-affected, mutant human hepatocytes is useful for the investigation of the molecular, biochemical, and phenotypic differences induced by that mutation. Read More

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http://dx.doi.org/10.1002/jimd.12067DOI Listing

Concerning "Triheptanoin vs trioctanoin for long-chain fatty acid oxidation disorders: A double blinded, randomized controlled trial" by Gillingham et al.

Authors:
John M Shoffner

J Inherit Metab Dis 2019 Mar 5. Epub 2019 Mar 5.

Neurology, Biochemical Genetics, Molecular Genetics, Atlanta, GA.

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http://dx.doi.org/10.1002/jimd.12078DOI Listing

A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia.

J Inherit Metab Dis 2019 Mar 5. Epub 2019 Mar 5.

Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California.

The enzyme carbamoyl phosphate synthetase 1 (CPS1; EC 6.3.4. Read More

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http://dx.doi.org/10.1002/jimd.12048DOI Listing
March 2019
3 Reads

Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program.

J Inherit Metab Dis 2019 Mar 4. Epub 2019 Mar 4.

BioMarin Pharmaceutical Inc., Novato, California, USA.

The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 μg/mg and ≥200 μg/mg creatinine (low- and high-uGAG) who had received galsulfase for ≥6 months. Read More

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http://dx.doi.org/10.1002/jimd.12079DOI Listing
March 2019
3.365 Impact Factor

Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial.

J Inherit Metab Dis 2019 Mar 4. Epub 2019 Mar 4.

Department of Haematology, LSDU, Institute of Immunity and Transplantation, Royal Free London NHS Foundation Trust, London, UK.

Pegunigalsidase alfa, a novel PEGylated, covalently crosslinked form of α-galactosidase A developed as enzyme replacement therapy (ERT) for Fabry disease (FD), was designed to increase plasma half-life and reduce immunogenicity, thereby enhancing efficacy compared with available products. Symptomatic adults with FD participated in this open-label, 3-month dose-ranging study, followed by a 9-month extension. Three cohorts were enrolled in a stepwise manner, each receiving increased doses of pegunigalsidase alfa: 0. Read More

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http://dx.doi.org/10.1002/jimd.12080DOI Listing
March 2019
1 Read

Allogeneic hematopoietic cell transplantation in Farber disease.

J Inherit Metab Dis 2019 Mar 27;42(2):286-294. Epub 2019 Feb 27.

Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.

Background: Farber disease (FD) is a rare, lysosomal storage disorder caused by deficient acid ceramidase activity. FD has long been considered a fatal disorder with death in the first three decades of life resulting either from respiratory insufficiency as a consequence of airway involvement or from progressive neurodegeneration because of nervous system involvement. Peripheral symptoms associated with FD, including inflammatory joint disease, have been described to improve relatively rapidly after hematopoietic cell transplantation (HCT). Read More

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http://dx.doi.org/10.1002/jimd.12043DOI Listing
March 2019
3 Reads

Movement disorders and nonmotor neuropsychological symptoms in children and adults with classical galactosemia.

J Inherit Metab Dis 2019 Jan 12. Epub 2019 Jan 12.

Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Although movement disorders (MDs) are known complications, the exact frequency and severity remains uncertain in patients with classical galactosemia, especially in children. We determined the frequency, classification and severity of MDs in a cohort of pediatric and adult galactosemia patients, and assessed the association with nonmotor neuropsychological symptoms and daily functioning. Patients from seven centers in the United Kingdom and the Netherlands with a confirmed galactosemia diagnosis were invited to participate. Read More

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http://dx.doi.org/10.1002/jimd.12054DOI Listing
January 2019
2 Reads

Response to Letter to the editor.

J Inherit Metab Dis 2019 Feb 22. Epub 2019 Feb 22.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1002/jimd.12077DOI Listing
February 2019

The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy.

J Inherit Metab Dis 2019 Mar 21;42(2):303-312. Epub 2019 Feb 21.

Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Introduction: Currently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C -bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment. Read More

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http://doi.wiley.com/10.1002/jimd.12042
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http://dx.doi.org/10.1002/jimd.12042DOI Listing
March 2019
7 Reads

An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency.

J Inherit Metab Dis 2019 Jan 12. Epub 2019 Jan 12.

MRC Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.

Riboflavin transporter deficiency (RTD) is a rare neurological condition that encompasses the Brown-Vialetto-Van Laere and Fazio-Londe syndromes since the discovery of pathogenic mutations in the SLC52A2 and SLC52A3 genes that encode human riboflavin transporters RFVT2 and RFVT3. Patients present with a deteriorating progression of peripheral and cranial neuropathy that causes muscle weakness, vision loss, deafness, sensory ataxia, and respiratory compromise which when left untreated can be fatal. Considerable progress in the clinical and genetic diagnosis of RTDs has been made in recent years and has permitted the successful lifesaving treatment of many patients with high dose riboflavin supplementation. Read More

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http://dx.doi.org/10.1002/jimd.12053DOI Listing
January 2019
1 Read

Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.

J Inherit Metab Dis 2019 Mar 17;42(2):333-352. Epub 2019 Feb 17.

Inherited Metabolic Diseases Clinic, Section of Clinical Genetics and Metabolism, University of Colorado Denver, Aurora, Colorado.

Aim: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry.

Results: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. Read More

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http://dx.doi.org/10.1002/jimd.12041DOI Listing
March 2019
10 Reads

New insights into human lysine degradation pathways with relevance to pyridoxine-dependent epilepsy due to antiquitin deficiency.

J Inherit Metab Dis 2019 Feb 14. Epub 2019 Feb 14.

Division of Child Neurology, University Children's Hospital Zurich, Zurich, Switzerland.

Deficiency of antiquitin (ATQ), an enzyme involved in lysine degradation, is the major cause of vitamin B -dependent epilepsy. Accumulation of the potentially neurotoxic α-aminoadipic semialdehyde (AASA) may contribute to frequently associated developmental delay. AASA is formed by α-aminoadipic semialdehyde synthase (AASS) via the saccharopine pathway of lysine degradation, or, as has been postulated, by the pipecolic acid (PA) pathway, and then converted to α-aminoadipic acid by ATQ. Read More

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http://doi.wiley.com/10.1002/jimd.12076
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http://dx.doi.org/10.1002/jimd.12076DOI Listing
February 2019
12 Reads

Neurometabolic Hereditary Diseases of Adults.

Authors:
Georg F Hoffmann

J Inherit Metab Dis 2019 Feb 13. Epub 2019 Feb 13.

University Children's Hospital, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.

Springer International Publishing AG 2018, ISBN 978-3-319-76148-0, ISBN 978-3-319-76148-0 (ebook) Growing up is a fascinating journey. The book "Neurometabolic Hereditary Diseases of Adults" designed and edited by Dr. Allessandro P. Read More

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http://doi.wiley.com/10.1002/jimd.12074
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http://dx.doi.org/10.1002/jimd.12074DOI Listing
February 2019
6 Reads

The clinical presentation of cobalamin-related disorders: From acquired deficiencies to inborn errors of absorption and intracellular pathways.

J Inherit Metab Dis 2018 Dec 27. Epub 2018 Dec 27.

Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, Zürich, Switzerland.

This review gives an overview of clinical characteristics, treatment and outcome of nutritional and acquired cobalamin (Cbl; synonym: vitamin B12) deficiencies, inborn errors of Cbl absorption and intracellular trafficking, as well as methylenetetrahydrofolate dehydrogenase (MTHFD1) and methylene tetrahydrofolate reductase (MTHFR) deficiencies, which impair Cbl-dependent remethylation. Acquired and inborn Cbl-related disorders and MTHFR deficiency cause multisystem, often severe disease. Failure to thrive, neurocognitive or psychiatric symptoms, eye disease, bone marrow alterations, microangiopathy and thromboembolic events are characteristic. Read More

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http://dx.doi.org/10.1002/jimd.12012DOI Listing
December 2018
2 Reads

Impact of newborn screening for very-long-chain acyl-CoA dehydrogenase deficiency on genetic, enzymatic, and clinical outcomes.

J Inherit Metab Dis 2019 Feb 13. Epub 2019 Feb 13.

Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.

Most infants with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. If this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms, is unclear. Therefore, a 10-year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS was conducted. Read More

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http://dx.doi.org/10.1002/jimd.12075DOI Listing
February 2019
10 Reads

Clinical, neuroradiological, and biochemical features of SLC35A2-CDG patients.

J Inherit Metab Dis 2019 Jan 12. Epub 2019 Jan 12.

Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.

SLC35A2-CDG is caused by mutations in the X-linked SLC35A2 gene encoding the UDP-galactose transporter. SLC35A2 mutations lead to hypogalactosylation of N-glycans. SLC35A2-CDG is characterized by severe neurological symptoms and, in many patients, early-onset epileptic encephalopathy. Read More

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http://dx.doi.org/10.1002/jimd.12055DOI Listing
January 2019
3 Reads

Biotin in metabolism, gene expression, and human disease.

J Inherit Metab Dis 2019 Feb 11. Epub 2019 Feb 11.

Programa de Investigación en Cáncer de Mama and Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.

Biotin is a water-soluble vitamin that belongs to the vitamin B complex and which is an essential nutrient of all living organisms from bacteria to man. In eukaryotic cells biotin functions as a prosthetic group of enzymes, collectively known as biotin-dependent carboxylases that catalyze key reactions in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Enzyme-bound biotin acts as a vector to transfer a carboxyl group between donor and acceptor molecules during carboxylation reactions. Read More

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http://dx.doi.org/10.1002/jimd.12073DOI Listing
February 2019

Pharmacokinetics, pharmacodynamics, and safety of moss-aGalactosidase A in patients with Fabry disease.

J Inherit Metab Dis 2019 Jan 12. Epub 2019 Jan 12.

Greenovation Biotech GmbH, Freiburg, Germany.

Moss-aGalactosidase A (moss-aGal) is a moss-derived version of human α-galactosidase developed for enzyme replacement therapy in patients with Fabry disease. It exhibits a homogenous N-glycosylation profile with >90% mannose-terminated glycans. In contrast to mammalian cell produced α-galactosidase, moss-aGal does not rely on mannose-6-phosphate receptor mediated endocytosis but targets the mannose receptor for tissue uptake. Read More

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http://dx.doi.org/10.1002/jimd.12052DOI Listing
January 2019
7 Reads

Long-term evaluation of urinary copper excretion and non-caeruloplasmin associated copper in Wilson disease patients under medical treatment.

J Inherit Metab Dis 2019 Mar 11;42(2):371-380. Epub 2019 Feb 11.

Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany.

Objective: Urinary copper excretion rates and non-caeruloplasmin associated copper concentrations are increased in patients with Wilson disease. However, there is little literature describing the monitoring of these parameters over the long term.

Methods: This is a monocentric retrospective study including data collected between 2003 and 2015 from 321 patients with Wilson disease by chart review. Read More

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http://dx.doi.org/10.1002/jimd.12046DOI Listing
March 2019
1 Read

Allogeneic hematopoietic stem cell transplantation with myeloablative conditioning for adult cerebral X-linked adrenoleukodystrophy.

J Inherit Metab Dis 2019 Mar 11;42(2):313-324. Epub 2019 Feb 11.

Department Pediatric Oncology/Hematology/SCT, Charité Campus Virchow-Klinikum, Berlin, Germany.

The adult cerebral form of X-linked adrenoleukodystrophy (ACALD), an acute inflammatory demyelinating disease, results in a rapidly progressive neurodegeneration, typically leading to severe disability or death within a few years after onset. We have treated 15 men who had developed ACALD with allogeneic hematopoietic stem cell transplantation (HSCT) from matched donors after myeloablative conditioning with busulfan and cyclophosphamide. All patients engrafted and 11 survived (estimated survival 73 ± 11%), 8 with stable cognition and 7 of them with stable motor function (estimated event-free survival 36 ± 17%). Read More

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http://dx.doi.org/10.1002/jimd.12044DOI Listing
March 2019
2 Reads

Influence of implementing a protocol for an intravenously administered ammonia scavenger on the management of acute hyperammonemia in a pediatric intensive care unit.

J Inherit Metab Dis 2019 Jan;42(1):77-85

Pediatric Intensive Care Unit, Department of Pediatrics, CHU Sainte-Justine and Université de Montréal, Montreal, Canada.

The purpose of the study was to evaluate the influence of establishing a protocol for the use of combined sodium benzoate and sodium phenylacetate (SBSP) (Ammonul®) to treat acute hyperammonemia. This was a retrospective, single-center study in a 24-bed medical and surgical pediatric intensive care unit (PICU) in a tertiary care teaching maternal-child hospital in Canada. Inclusion criteria were age < 18 years, PICU admission between 1 January 2000 and 30 June 2016, and SBSP treatment. Read More

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http://dx.doi.org/10.1002/jimd.12029DOI Listing
January 2019
3 Reads

Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: Update of 34 patients.

J Inherit Metab Dis 2019 Jan;42(1):147-158

Metabolic Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.

Background: Transaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation.

Methods: We performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. Read More

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http://dx.doi.org/10.1002/jimd.12036DOI Listing
January 2019
4 Reads

Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review.

J Inherit Metab Dis 2019 Jan;42(1):29-48

Portuguese Association for CDG, Lisbon, Portugal.

Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction. Read More

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http://dx.doi.org/10.1002/jimd.12025DOI Listing
January 2019
1 Read

Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort.

J Inherit Metab Dis 2019 Jan;42(1):107-116

Department of Human Genetics, McGill University, Montreal, Quebec, Canada.

Background: The clinical significance of combined malonic and methylmalonic aciduria due to ACSF3 deficiency (CMAMMA) is controversial. In most publications, affected patients were identified during the investigation of various complaints.

Methods: Using a cross-sectional multicenter retrospective natural history study, we describe the course of all known CMAMMA individuals in the province of Quebec. Read More

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http://dx.doi.org/10.1002/jimd.12032DOI Listing
January 2019

The phenotype modifier: is the mitochondrial DNA background responsible for individual differences in disease severity.

J Inherit Metab Dis 2019 Jan;42(1):3-4

Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1002/jimd.12050DOI Listing
January 2019

Proposal for an individualized dietary strategy in patients with very long-chain acyl-CoA dehydrogenase deficiency.

J Inherit Metab Dis 2019 Jan;42(1):159-168

Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center, Wilhelmina Children's Hospital (UMCU), University Medical Center Utrecht, Internal Mail KE 04.306.0, PO Box 85090 3508 AB, Utrecht, Netherlands.

Background: Patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments.

Objective: To define dietary strategies for individuals with VLCADD based on the predicted phenotype. Read More

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http://dx.doi.org/10.1002/jimd.12037DOI Listing
January 2019
3 Reads

Inborn errors of coenzyme A metabolism and neurodegeneration.

J Inherit Metab Dis 2019 Jan;42(1):49-56

Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute C. Besta, Via Temolo 4, Milan 20126, Italy.

Two inborn errors of coenzyme A (CoA) metabolism are responsible for distinct forms of neurodegeneration with brain iron accumulation (NBIA), a heterogeneous group of neurodegenerative diseases having as a common denominator iron accumulation mainly in the inner portion of globus pallidus. Pantothenate kinase-associated neurodegeneration (PKAN), an autosomal recessive disorder with progressive impairment of movement, vision and cognition, is the most common form of NBIA and is caused by mutations in the pantothenate kinase 2 gene (PANK2), coding for a mitochondrial enzyme, which phosphorylates vitamin B5 in the first reaction of the CoA biosynthetic pathway. Another very rare but similar disorder, denominated CoPAN, is caused by mutations in coenzyme A synthase gene (COASY) coding for a bi-functional mitochondrial enzyme, which catalyzes the final steps of CoA biosynthesis. Read More

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http://dx.doi.org/10.1002/jimd.12026DOI Listing
January 2019

Patterns, evolution, and severity of striatal injury in insidious- vs acute-onset glutaric aciduria type 1.

J Inherit Metab Dis 2019 Jan;42(1):117-127

Department of Neuroradiology, University of Heidelberg Medical Center, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.

Background: Striatal injury in patients with glutaric aciduria type 1 (GA1) results in a complex, predominantly dystonic, movement disorder. Onset may be acute following acute encephalopathic crisis (AEC) or insidious without apparent acute event.

Methods: We analyzed clinical and striatal magnetic resonance imaging (MRI) findings in 21 symptomatic GA1 patients to investigate if insidious- and acute-onset patients differed in timing, pattern of striatal injury, and outcome. Read More

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http://dx.doi.org/10.1002/jimd.12033DOI Listing
January 2019
1 Read

Identification and characterization of 40 novel hydroxymethylbilane synthase mutations that cause acute intermittent porphyria.

J Inherit Metab Dis 2019 Jan;42(1):186-194

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue Room 14-34, New York, NY 10029, USA.

Acute intermittent porphyria (AIP), an autosomal dominant disorder due to the half-normal activity of hydroxymethylbilane synthase (HMBS), is characterized by acute neurovisceral attacks that are precipitated by factors that induce heme biosynthesis. Molecular diagnosis is the most sensitive and specific diagnostic test for AIP, and importantly, it permits the identification of asymptomatic family members for genetic counseling and avoidance of precipitating factors. Here, we report the identification of 40 novel HMBS mutations, including 11 missense, four nonsense, 16 small insertions or deletions, eight consensus splice site mutations, and a complex insertion-deletion mutation in unrelated individuals with AIP. Read More

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http://dx.doi.org/10.1002/jimd.12040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162174PMC
January 2019
2 Reads

Results from a 78-week, single-arm, open-label phase 2 study to evaluate UX007 in pediatric and adult patients with severe long-chain fatty acid oxidation disorders (LC-FAOD).

J Inherit Metab Dis 2019 Jan;42(1):169-177

Ultragenyx Pharmaceutical Inc., Novato, California, USA.

Long-chain fatty acid oxidation disorders (LC-FAOD) are rare disorders characterized by acute crises of energy metabolism and severe energy deficiency that may present with cardiomyopathy, hypoglycemia, and/or rhabdomyolysis, which can lead to frequent hospitalizations and early death. An open-label Phase 2 study evaluated the efficacy of UX007, an investigational odd-carbon medium-chain triglyceride, in 29 subjects with severe LC-FAOD. UX007 was administered over 78 weeks at a target dose of 25-35% total daily caloric intake (mean 27. Read More

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http://dx.doi.org/10.1002/jimd.12038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348052PMC
January 2019
1 Read

The effectiveness of enzyme replacement therapy for juvenile-onset Pompe disease: A systematic review.

J Inherit Metab Dis 2019 Jan;42(1):57-65

Adelaide Health Technology Assessment, University of Adelaide, Adelaide, Level 9, AHMS Building, North Terrace 5005, South Australia, Australia.

Aim: The objective of this research was to determine the effectiveness of enzyme replacement therapy for juvenile-onset Pompe disease (patients aged 2 to 18 years at symptom onset) by systematic review.

Methods: A systematic search was conducted according to a protocol designed a priori of bibliographic databases and search engines. Studies selected according to pre-specified criteria were assessed for quality and risk of bias using standardised appraisal tools. Read More

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http://dx.doi.org/10.1002/jimd.12027DOI Listing
January 2019