5,030 results match your criteria Journal of Inherited Metabolic Disease [Journal]


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 Feb 17. 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
February 2019

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.

Background: 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 (AAA) 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
3 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
2 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
1 Read

Impact of NBS for VLCAD 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.

Background: 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.

Methods: A 10 year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS. Read More

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http://dx.doi.org/10.1002/jimd.12075DOI Listing
February 2019
2 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
1 Read

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 y, 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 (Wolf 2001). Enzyme-bound biotin acts as a vector to transfer a carboxyl group between donor and acceptor molecules during carboxylation reactions (León-Del-Rio et al. 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

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

J Inherit Metab Dis 2019 Feb 11. 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
February 2019

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

J Inherit Metab Dis 2019 Feb 11. 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
February 2019

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
1 Read

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
1 Read

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

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

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
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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
January 2019
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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
January 2019
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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

Newborn screening for homocystinurias: Recent recommendations versus current practice.

J Inherit Metab Dis 2019 Jan;42(1):128-139

Austrian Newborn Screening, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Purpose: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations.

Methods: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Read More

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http://dx.doi.org/10.1002/jimd.12034DOI Listing
January 2019
7 Reads

The decision to discontinue screening for carnitine uptake disorder in New Zealand.

J Inherit Metab Dis 2019 Jan;42(1):86-92

Newborn Metabolic Screening Programme, LabPlus, Auckland City Hospital, Auckland, New Zealand.

When screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn screening (NBS) service identified infants as screen-positive if they had initial and repeat free carnitine (C0) levels of less than 5.0 μmol/L. Since 2006, the NBS service has identified two infants with biochemical and genetic features consistent with neonatal CUD and nine mothers with features consistent with maternal CUD. Read More

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http://dx.doi.org/10.1002/jimd.12030DOI Listing
January 2019

Inhibiting PNP for the therapy of hyperuricemia in Lesch-Nyhan disease: Preliminary in vitro studies with analogues of immucillin-G.

J Inherit Metab Dis 2019 Jan;42(1):178-185

Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy.

Lesch-Nyhan disease (LND) is a rare X-linked genetic disorder, with complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency, uric acid (UA), hypoxanthine and xanthine accumulation, and a devastating neurologic syndrome. UA excess, causing renal failure, is commonly decreased by xanthine oxidoreductase (XOR) inhibitors, such as allopurinol, yielding a xanthine and hypoxanthine increase. Xanthine accumulation may result in renal stones, while hypoxanthine excess seems involved in the neurological disorder. Read More

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http://dx.doi.org/10.1002/jimd.12039DOI Listing
January 2019
1 Read

Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review.

J Inherit Metab Dis 2019 Jan;42(1):66-76

Faculty of Ceilândia, University of Brasília, Brasília, Brazil.

Introduction: Mucopolysaccharidosis VI is a rare disease characterized by the arylsulfatase B enzyme deficiency, which is responsible for different clinical manifestations. The treatment consists of enzyme replacement therapy with intravenous administration of galsulfase.

Objective: Evaluate the effectiveness of the enzyme replacement therapy with galsulfase for the mucopolysaccharidosis VI treatment. Read More

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http://dx.doi.org/10.1002/jimd.12028DOI Listing
January 2019

On being an editor, reviewer, and author-different sides of the same coin.

J Inherit Metab Dis 2019 Jan;42(1):1-2

Center for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, Heidelberg, Germany.

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http://dx.doi.org/10.1002/jimd.12017DOI Listing
January 2019

Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening.

J Inherit Metab Dis 2019 Jan;42(1):140-146

Division of Human Genetics, The Children's Hospital of Philadelphia, Colket Translational Research Building, 3501 Civic Center Blvd, Floor 9, 19104, Philadelphia, Pennsylvania, USA.

Background: Glutamate formiminotransferase deficiency (FTCD deficiency) or formiminoglutamic aciduria is the second most common of the known inherited disorders of folate metabolism. Initial case reports suggested that patients may have severe intellectual disability and megaloblastic anemia. However, these cases were obtained from screening cohorts of patients with developmental delay. Read More

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http://dx.doi.org/10.1002/jimd.12035DOI Listing
January 2019
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International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.

J Inherit Metab Dis 2019 Jan;42(1):5-28

Department of Clinical Genomics, Mayo Clinic, Rochester, New York.

Phosphomannomutase 2 (PMM2-CDG) is the most common congenital disorder of N-glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2-CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach. Read More

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http://dx.doi.org/10.1002/jimd.12024DOI Listing
January 2019
1 Read

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders-A successful strategy for clinical research of rare diseases.

J Inherit Metab Dis 2019 Jan;42(1):93-106

Centre for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Inherited Metabolic Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 430 69120, Heidelberg, Germany.

Background: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts.

Aims: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs.

Methods: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. Read More

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http://doi.wiley.com/10.1002/jimd.12031
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http://dx.doi.org/10.1002/jimd.12031DOI Listing
January 2019
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Brain imaging in classic nonketotic hyperglycinemia: quantitative analysis and relation to phenotype.

J Inherit Metab Dis 2019 Feb 9. Epub 2019 Feb 9.

Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, Colorado, USA.

Objective: Patients with severe nonketotic hyperglycinemia have absent psychomotor development and intractable epilepsy, whereas attenuated patients have variable psychomotor development and absent or treatable epilepsy; differences in brain MRI between phenotypes have not been reported.

Methods: In a retrospective cross-sectional study, we reviewed 38 MRI studies from 24 molecularly proven nonketotic hyperglycinemia patients, and two transient nonketotic hyperglycinemia patients. Quantitative analyses included corpus callosum size, apparent diffusion coefficient, automated brain volumetric analysis, and glycine/creatine ratio by spectroscopy. Read More

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http://dx.doi.org/10.1002/jimd.12072DOI Listing
February 2019

Evaluation of dietary treatment and amino acid supplementation in organic acidurias and urea-cycle disorders.

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

Erasmus MC University Medical Center, Rotterdam, Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, the Netherlands.

Introduction: Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels.

Method: We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. Read More

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http://dx.doi.org/10.1002/jimd.12066DOI Listing
February 2019
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Development and feasibility of the use of an assessment tool measuring treatment efficacy in patients with trimethylaminuria: A mixed methods study.

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

Faculty of Health, Social Care and Education, Kingston University and St George's, University of London, London, UK.

Trimethylaminuria (TMAU) is a rare metabolic condition characterised by an unpleasant smell resembling rotting fish. Currently, the only measure of treatment efficacy is urine trimethylamine levels which do not always reflect the patient's experience of symptoms. A literature review did not find a specific tool to assess treatment efficacy from the patient's perspective. Read More

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http://doi.wiley.com/10.1002/jimd.12023
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http://dx.doi.org/10.1002/jimd.12023DOI Listing
February 2019
3 Reads

Synaptic energy metabolism and neuronal excitability, in sickness and in health.

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

Laboratory of Developmental Neurobiology, The Rockefeller University, New York, USA.

Most of the energy produced in the brain is dedicated to supporting synaptic transmission. Glucose is the main fuel, providing energy and carbon skeletons to the cells that execute and support synaptic function: neurons and astrocytes, respectively. It is unclear, however, how glucose is provided to and used by these cells under different levels of synaptic activity. Read More

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http://dx.doi.org/10.1002/jimd.12071DOI Listing
February 2019

Hepatic glutamine synthetase augmentation enhances ammonia detoxification.

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

Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.

The urea cycle and glutamine synthetase (GS) are the two main pathways for waste nitrogen removal and their deficiency results in hyperammonemia. Here, we investigated the efficacy of liver-specific GS overexpression for therapy of hyperammonemia. To achieve hepatic GS overexpression, we generated a helper-dependent adenoviral (HDAd) vector expressing the murine GS under the control of a liver-specific expression cassette (HDAd-GS). Read More

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http://dx.doi.org/10.1002/jimd.12070DOI Listing
February 2019

Argininosuccinic aciduria: Recent pathophysiological insights and therapeutic prospects.

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

Division of Metabolism and Children Research Centre (CRC), University Children's Hospital, Zurich, Switzerland.

The first patients affected by argininosuccinic aciduria (ASA) were reported 60 years ago. The clinical presentation was initially described as similar to other urea cycle defects, but increasing evidence has shown overtime an atypical systemic phenotype with a paradoxical observation, that is, a higher rate of neurological complications contrasting with a lower rate of hyperammonaemic episodes. The disappointing long-term clinical outcomes of many of the patients have challenged the current standard of care and therapeutic strategy, which aims to normalize plasma ammonia and arginine levels. Read More

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http://dx.doi.org/10.1002/jimd.12047DOI Listing
February 2019

Translational Metabolism: A multidisciplinary approach towards precision diagnosis of inborn errors of metabolism in the omics era.

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

Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

The laboratory diagnosis of inborn errors of metabolism has been revolutionized in recent years, thanks to the amazing developments in the field of DNA sequencing including whole exome and whole genome sequencing (WES and WGS). Interpretation of the results coming from WES and/or WGS analysis is definitely not trivial especially since the biological relevance of many of the variants identified by WES and/or WGS, have not been tested experimentally and prediction programs like POLYPHEN-2 and SIFT are far from perfect. Correct interpretation of WES and/or WGS results can only be achieved by performing functional studies at multiple levels (different metabolomics platforms, enzymology, in vitro and in vivo flux analysis), often requires studies in model organisms like zebra fish, Caenorhabditis elegans, Saccharomyces cerevisiae, mutant mice and others, and also requires the input of many different disciplines to make this Translational Metabolism approach effective. Read More

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http://dx.doi.org/10.1002/jimd.12008DOI Listing
December 2018
2 Reads

Growth impairment in individuals with citrin deficiency.

J Inherit Metab Dis 2019 Jan 9. Epub 2019 Jan 9.

Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.

Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD), and adult-onset type II citrullinemia (CTLN2). Owing to a defect in the NADH-shuttle, citrin deficiency impairs hepatic glycolysis and de novo lipogenesis leading to hepatic energy deficit. To investigate the physiological role of citrin, we studied the growth of 111 NICCD-affected subjects (51 males and 60 females) and 12 NICCD-unaffected subjects (five males and seven females), including the body weight, height, and genotype. Read More

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http://dx.doi.org/10.1002/jimd.12051DOI Listing
January 2019
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Fetal gene therapy for neurodegenerative lysosomal storage diseases.

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

Gene Transfer Technology Group, Institute for Women's Health, University College London, London, UK.

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http://dx.doi.org/10.1002/jimd.12018DOI Listing
December 2018
3.365 Impact Factor

An evolutionary approach to optimizing glucose-6-phosphatase-α enzymatic activity for gene therapy of glycogen storage disease type Ia.

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

Section on Cellular Differentiation, Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.

Glycogen storage disease type-Ia (GSD-Ia), caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), is characterized by impaired glucose homeostasis with a hallmark hypoglycemia, following a short fast. We have shown that G6pc-deficient (G6pc-/-) mice treated with recombinant adeno-associated virus (rAAV) vectors expressing either wild-type (WT) (rAAV-hG6PC-WT) or codon-optimized (co) (rAAV-co-hG6PC) human (h) G6Pase-α maintain glucose homeostasis if they restore ≥3% of normal hepatic G6Pase-α activity. The codon-optimized vector, which has a higher potency, is currently being used in a phase I/II clinical trial for human GSD-Ia (NCT 03517085). Read More

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http://dx.doi.org/10.1002/jimd.12069DOI Listing
February 2019
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Comprehensive characterization of ureagenesis in the spf mouse, a model of human OTC deficiency, reveals age-dependency of ammonia detoxification.

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

Division of Metabolism and Children's Research Centre (CRC), University Children's Hospital Zurich, Zurich, Switzerland.

The most common ureagenesis defect is X-linked ornithine transcarbamylase (OTC) deficiency which is a main target for novel therapeutic interventions. The spf mouse model carries a variant (c.386G>A, p. Read More

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http://dx.doi.org/10.1002/jimd.12068DOI Listing
February 2019

Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria.

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

Department of Pediatrics, Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg, Heidelberg, Germany.

Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38. Read More

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http://dx.doi.org/10.1002/jimd.12049DOI Listing
February 2019

Factor VIII and vWF deficiency in STT3A-CDG.

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

Department of Pediatrics, Division of Medical Genetics, University of Washington, Seattle, Western Australia.

STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern. All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p. Read More

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http://dx.doi.org/10.1002/jimd.12021DOI Listing
December 2018
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3.365 Impact Factor

Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect.

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

Department of Pediatrics, Division of Metabolism, Hacettepe University Faculty of Medicine, Ankara, Turkey.

MBOAT7 gene codes O-acyltransferase domain containing seven proteins which is one of four enzymes involved in remodeling of phosphoinositol phosphate (PIP) in LANDs cycle. We present clinical, neuroimaging, and genetic findings of 12 patients from 7 families with MBOAT7 gene defect, a recently defined novel phospholipid remodelling disease. To the best of our knowledge, our case series is the second report on patients with MBOAT7 gene defect. Read More

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http://dx.doi.org/10.1002/jimd.12016DOI Listing
December 2018
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Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis-A cross-sectional study.

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

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.

Galactosialidosis (GS; OMIM #256540) is a rare multisystemic inborn glycoprotein storage disease caused by biallelic mutations in the cathepsin A gene resulting in combined deficiency of the lysosomal enzymes β-galactosidase and α-neuraminidase. The precise understanding of the natural course of the disease is limited. Development of enzyme replacement therapy is at the preclinical stage. Read More

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http://doi.wiley.com/10.1002/jimd.12010
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http://dx.doi.org/10.1002/jimd.12010DOI Listing
December 2018
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Vitamin B , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation.

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

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

Vitamin B (cobalamin, Cbl) is a nutrient essential to human health. Due to its complex structure and dual cofactor forms, Cbl undergoes a complicated series of absorptive and processing steps before serving as cofactor for the enzymes methylmalonyl-CoA mutase and methionine synthase. Methylmalonyl-CoA mutase is required for the catabolism of certain (branched-chain) amino acids into an anaplerotic substrate in the mitochondrion, and dysfunction of the enzyme itself or in production of its cofactor adenosyl-Cbl result in an inability to successfully undergo protein catabolism with concomitant mitochondrial energy disruption. Read More

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http://dx.doi.org/10.1002/jimd.12009DOI Listing
December 2018

Focal cerebellar infarction as an initial sign of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

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

Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a type of mitochondrial disorder and stroke-like lesions are observed prominently in the brain magnetic resonance imaging. Those stroke-like lesions of MELAS patients are usually located in the posterior quadrants and do not correspond to typical vascular territories. This case illustrates that focal cerebellar infarction can be the sole initial sign of MELAS. Read More

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http://dx.doi.org/10.1002/jimd.12020DOI Listing
December 2018
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The neurological and psychological phenotype of adult patients with early-treated phenylketonuria: a systematic review.

J Inherit Metab Dis 2019 Jan 28. Epub 2019 Jan 28.

Division of Inborn Metabolic Diseases, Department of Paediatrics, University Hospital, Padua, Italy.

Newborn screening for phenylketonuria and early introduction of dietary therapy has been remarkably successful in preventing the severe neurological features of phenylketonuria, including mental retardation and epilepsy. However, concerns remain that long-term outcome is still suboptimal, particularly in adult patients who are no longer on strict phenylalanine-restricted diets. With our systematic literature review we aimed to describe the neurological phenotype of adults with early-treated phenylketonuria (ETPKU). Read More

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http://dx.doi.org/10.1002/jimd.12065DOI Listing
January 2019
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Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome.

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

Rappaport Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel.

Mitochondrial aconitase is the second enzyme in the tricarboxylic acid (TCA) cycle catalyzing the interconversion of citrate into isocitrate and encoded by the nuclear gene ACO2. A homozygous pathogenic variant in the ACO2 gene was initially described in 2012 resulting in a novel disorder termed "infantile cerebellar retinal degeneration" (ICRD, OMIM#614559). Subsequently, additional studies reported patients with pathogenic ACO2 variants, further expanding the genetic and clinical spectrum of this disorder to include milder and later onset manifestations. Read More

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http://dx.doi.org/10.1002/jimd.12022DOI Listing
December 2018
3.365 Impact Factor

Opening a window on lysosomal acid lipase deficiency: biochemical, molecular and epidemiological insights.

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

Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Naples, Italy.

Objective: Lysosomal acid lipase deficiency (LAL-D) is a multi-organ autosomal recessive disease caused by mutations in LIPA.

Study Design: We reviewed data from 681 samples (white blood cells (WBC) n=625, fibroblasts =30, liver =4, amniocytes =13, chorionic villus =9) received for analysis of lysosomal acid lipase (LAL) activity over a 15-year period. LIPA sequencing was performed in 49 patients with reduced (n=26) or deficient (n=23) LAL activity. Read More

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http://dx.doi.org/10.1002/jimd.12057DOI Listing
January 2019

Choline-related-inherited metabolic diseases-A mini review.

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

University Childrens Hospital, Paracelsus Medical University (PMU) Salzburg, Salzburg, Austria.

In humans, the important water soluble, vitamin-like nutrient choline, is taken up with the diet or recycled in the liver. Deficiencies of choline have only been reported in experimental situations or total parenteral nutrition. Currently, no recommended dietary allowances are published; only an adequate daily intake is defined. Read More

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http://doi.wiley.com/10.1002/jimd.12011
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http://dx.doi.org/10.1002/jimd.12011DOI Listing
December 2018
3 Reads