Search Our Scientific Publications & Authors

J Appl Res Intellect Disabil 2019 Apr 15. Epub 2019 Apr 15.

Section for Neuropediatrics and Inborn Errors of Metabolism, University Children's Hospital, Clinic I, Heidelberg, Germany.

Background: Caring for a child with intellectual disability (ID) has been associated with increased social and psychological burdens. Diagnostic and prognostic uncertainty may enhance emotional stress in families.

Method: The present authors assessed the motivations, expectations, mental health, physical health and the quality of life of 194 parents whose children with intellectual disability were undergoing a genetic diagnostic workup. Read More

J Pediatr Gastroenterol Nutr 2019 Apr 1. Epub 2019 Apr 1.

Department of Pediatrics, University of Torino.

Liver transplant (LT) is a therapeutic option for a growing number of inborn errors of metabolism (IEM), including some disorders not confined to the liver. Clinical advantages of LT in maple syrup urine disease (MSUD), methylmalonic acidemia (MMA), and argininosuccinic aciduria (ASA) have been reported. However, no information on the early metabolic effect of LT after portal reperfusion is available in these disorders. Read More

J Pharm Sci 2019 Apr 5. Epub 2019 Apr 5.

Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia. Electronic address:

Mucopolysaccharidosis IVA (MPS IVA or Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to lysosomal storage of keratan sulfate (KS) and chondroitin-6-sulfate. Currently, enzyme replacement therapy (ERT) using an enzyme produced in CHO cells represents the main treatment option for MPS IVA patients. As an alternative, we reported the production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme. Read More

Blood Purif 2019 Apr 3;47 Suppl 2:1-7. Epub 2019 Apr 3.

Department of Pediatrics, School of Medicine, Iwate Medical University, Morioka, Japan.

Background/ Aims: Owing to practical and technical developments, continuous renal replacement therapy (CRRT) has been administered even in critically ill neonates. In this study, the complications in CRRT for neonates were examined to establish a safe CRRT.

Methods: This retrospective study reviewed the clinical records of neonates who underwent CRRT at our neonatal intensive care unit between 2009 and 2017. Read More

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

Pediatr Neurol 2019 Feb 18. Epub 2019 Feb 18.

Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia; King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Electronic address:

Background: Tetrahydrobiopterin is an essential cofactor for the hydroxylation of aromatic amino acids phenylalanine, tyrosine, and tryptophan. Therefore, tetrahydrobiopterin deficiency results in hyperphenylalaninemia as well as dopamine and serotonin depletion in the central nervous system. The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes the second step of de novo synthesis of tetrahydrobiopterin, and its deficiency is the most frequent cause of tetrahydrobiopterin metabolism disorders. Read More

Paediatr Child Health 2018 Sep 16;23(6):403-419. Epub 2018 Aug 16.

Canadian Paediatric Society, Mental Health and Developmental Disabilities Committee, Ottawa, Ontario.

Global developmental delay (GDD) and intellectual disability (ID) are common concerns in the paediatric setting. Etiologies of both conditions are highly heterogeneous. The American Academy of Pediatrics, the American Academy of Neurology and the British Columbia-based Treatable Intellectual Disability Endeavor (TIDE) protocol have each proposed multitiered investigations of GDD/ID to guide physicians toward an understanding of etiology that optimizes therapeutic yield. Read More

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

Mov Disord 2019 Mar 26. Epub 2019 Mar 26.

Department of Neurogenetics, Kolling Institute, Royal North Shore Hospital and University of Sydney, St Leonards, NSW, Australia.

The term "cerebral palsy mimic" is used to describe a number of neurogenetic disorders that may present with motor symptoms in early childhood, resulting in a misdiagnosis of cerebral palsy. Cerebral palsy describes a heterogeneous group of neurodevelopmental disorders characterized by onset in infancy or early childhood of motor symptoms (including hypotonia, spasticity, dystonia, and chorea), often accompanied by developmental delay. The primary etiology of a cerebral palsy syndrome should always be identified if possible. Read More

Hepatology 2019 Mar 26. Epub 2019 Mar 26.

Robert Debré Hospital, University Paris Diderot-Sorbonne Paris Cité, APHP, Reference Center for Inherited Metabolic Diseases, Paris, FR.

Mitochondrial disease is concerning with rapid infantile liver failure. Two sibling pairs with variants in QIL1, a gene important for mitochondrial contact site and cristae organizing system (MICOS) function, were recently reported. They had intermittent liver disease, mild cardiac hypertrophy, cerebellar atrophy, acquired microcephaly, neurologic impairment and death before age 5 (12mo-5yo). Read More

Yonsei Med J 2019 04;60(4):401

Department of Pediatrics, Gangnam Severance Hospital, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.

Eur J Pediatr 2019 Mar 20. Epub 2019 Mar 20.

Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Gazi Yaşargil Training and Research Hospital, Diyarbakir, Turkey.

Several recent studies have reported that toxic metabolites accumulated in the body as a product of inborn errors of metabolism (IEM) are eliminated more rapidly with continuous venovenous hemodiafiltration (CVVHDF) than with peritoneal dialysis (PD). However, there is still uncertainty about the impacts of dialysis modalities on the short-term outcome. Here, it was aimed to investigate the effects of dialysis modalities on the short-term outcome. Read More

Epilepsia Open 2019 Mar 25;4(1):10-29. Epub 2019 Jan 25.

Clinical Neuroscience UCL-Institute of Child Health London UK.

The aim of this study was to evaluate whether specific etiologies of neonatal seizures have distinct ictal electroclinical features. A systematic review of English articles using the PubMed database since 2004 (last update 9/26/16). Search terms included text words and Medical Subject Headings (MeSH) terms related to neonatal seizures. Read More

Pediatr Nephrol 2019 Mar 6. Epub 2019 Mar 6.

Sections of Nephrology, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 245, Houston, TX, 77033, USA.

Background: Critically ill children have a high prevalence of malnutrition. Children with acute kidney injury experience high rates of protein debt. Previous research has indicated that protein provision is positively associated with survival. Read More

Metabolomics 2019 Feb 28;15(3):32. Epub 2019 Feb 28.

Institute of Clinical Chemistry, Inselspital, University Hospital Bern, 3010, Bern, Switzerland.

Introduction: A decline in mitochondrial function represents a key factor of a large number of inborn errors of metabolism, which lead to an extremely heterogeneous group of disorders.

Objectives: To gain insight into the biochemical consequences of mitochondrial dysfunction, we performed a metabolic profiling study in human skin fibroblasts using galactose stress medium, which forces cells to rely on mitochondrial metabolism.

Methods: Fibroblasts from controls, complex I and pyruvate dehydrogenase (PDH) deficient patients were grown under glucose or galactose culture condition. Read More

Metabolomics 2018 May 25;14(6):76. Epub 2018 May 25.

Clinical Biochemistry Department, Institut de Recerca Sant Joan de Déu, Barcelona, Spain.

Introduction: Amino acid analysis in biological fluids is essential for the study of inborn errors of metabolism (IEM) and other diseases.

Objectives: Our aim was to develop a UPLC-MS/MS procedure for the analysis of 25 amino acids and identification of 17 related compounds.

Methods: Sample treatment conditions were optimized for plasma, urine, cerebrospinal fluid (CSF) and dried blood spots. Read More

Indian Pediatr 2019 Feb;56(2):126-129

Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.

Objective: To find the strength of agreement between point-of-care and serum b-hydroxybutyrate.

Methods: 236 paired samples (capillary b-hydroxybutyrate by a point of care device and serum b-hydroxybutyrate by colorimetric enzymatic estimation) samples were collected from 26 children aged <13 years admitted with diabetic ketoacidosis. Inborn errors of metabolism and septic shock were excluded. Read More

Pediatr Clin North Am 2019 04;66(2):369-386

Division of Genetics, Genomics and Metabolic Disorders, Children's Hospital of Michigan, 3950 Beaubien Street, Detroit, MI 48201, USA; Department of Pediatrics, Wayne State University School of Medicine, 540 E Canfield #2375, Detroit, MI 48201, USA; Center for Molecular Medicine and Genetics and Department of Pathology, Wayne State University School of Medicine, 2375 Scott Hall, 540 East Canfield, Detroit, MI 48201, USA.

Newborn screening has evolved since its introduction in 1963. The disorders that are being screened for continue to evolve as new treatments and new technologies advance. In this review, the authors discuss the current state of newborn screening in the United States, including the disorders currently being screened for and how newborn screening is performed. Read More

PLoS One 2019 28;14(2):e0212458. Epub 2019 Feb 28.

Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Background And Aims: Inborn errors of purine and pyrimidine metabolism are a diverse group of disorders with possible serious or life-threatening symptoms. They may be associated with neurological symptoms, renal stone disease or immunodeficiency. However, the clinical presentation can be nonspecific and mild so that a number of cases may be missed. Read More

Transplantation 2019 Feb 18. Epub 2019 Feb 18.

Department of Paediatrics, Paediatric Gastroenterology and Hepatology unit, Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.

Background: Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.

Aim: This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months post-transplantation. The secondary objective included the assessment of safety up to 12 months post-infusion, and of preliminary efficacy. Read More

Clin Chim Acta 2019 May 13;492:69-71. Epub 2019 Feb 13.

Metabolic Laboratory, Center of Diagnostics, Hamburg, Germany; NCL Clinic, Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany. Electronic address:

Purpose: CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. CLN2 disease has recently become treatable by enzyme replacement, which can only be effective when the disease is diagnosed early. We have investigated the reliability of a test for TPP1 deficiency in dried blood specimens (DBS) to detect CLN2 disease. Read More

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

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

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

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

Ann Transl Med 2018 Dec;6(24):475

Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Primary mitochondrial disorders are a group of clinically variable and heterogeneous inborn errors of metabolism (IEMs), resulting from defects in cellular energy, and can affect every organ system of the body. Clinical presentations vary and may include symptoms of fatigue, skeletal muscle weakness, exercise intolerance, short stature, failure to thrive, blindness, ptosis and ophthalmoplegia, nystagmus, hearing loss, hypoglycemia, diabetes mellitus, learning difficulties, intellectual disability, seizures, stroke-like episodes, spasticity, dystonia, hypotonia, pain, neuropsychiatric symptoms, gastrointestinal reflux, dysmotility, gastrointestinal pseudo-obstruction, cardiomyopathy, cardiac conduction defects, and other endocrine, renal, cardiac, and liver problems. Most phenotypic manifestations are multi-systemic, with presentations varying at different age of onset and may show great variability within members of the same family; making these truly complex IEMs. Read More

Ann Transl Med 2018 Dec;6(24):474

Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Glucose is the main energy fuel for the human brain. Maintenance of glucose homeostasis is therefore, crucial to meet cellular energy demands in both - normal physiological states and during stress or increased demands. Glucose is stored as glycogen primarily in the liver and skeletal muscle with a small amount stored in the brain. Read More

Ann Transl Med 2018 Dec;6(24):473

Department of Pediatrics and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism due to disruption of either mitochondrial β-oxidation or the fatty acid transport using the carnitine transport pathway. The presentation of a FAOD will depend upon the specific disorder, but common elements may be seen, and ultimately require a similar treatment. Initial presentations of the FAODs in the neonatal period with severe symptoms include cardiomyopathy, while during infancy and childhood liver dysfunction and hypoketotic hypoglycemia are common. Read More

Ann Transl Med 2018 Dec;6(24):469

Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.

Inborn errors of metabolism (IEMs) are rare genetic or inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or impaired organelle function presenting as complicated medical conditions involving several human organ systems. They involve great complexity of the underlying pathophysiology, biochemical workup, and molecular analysis, and have complicated therapeutic options for management. Age of presentation can vary from infancy to adolescence with the more severe forms appearing in early childhood accompanied by significant morbidity and mortality. Read More

Ann Transl Med 2018 Dec;6(24):467

Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

The 21 century is an exciting time to be in the field of metabolic medicine. As with many fields, one of the keys to anticipating the future is to understand the past. The term "inborn error of metabolism" was first coined in 1908 by Sir Archibald Garrod, in reference to four disorders (alkaptonuria, pentosuria, cystinuria and albinism). Read More

Orphanet J Rare Dis 2019 01;14(1):32

Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.

Background: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Read More

J Inherit Metab Dis 2019 Mar 5;42(2):197-208. Epub 2019 Feb 5.

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

Pediatr Rev 2019 Feb;40(2):60-70

Department of Pediatrics, Baylor College of Medicine, and Advanced Heart Failure Unit, Texas Children's Hospital, Houston, TX.

Congestive heart failure is a final common clinical pathway for several diseases in childhood, such as familial cardiomyopathy, viral myocarditis, inborn errors of metabolism, and autoimmune disorders. Early identification and treatment can reduce symptom severity and may affect outcomes. In this review, the clinical characteristics of pediatric heart failure are described, and the initial diagnostic evaluation is outlined. Read More

East Mediterr Health J 2019 Jan 23;24(11):1103-1111. Epub 2019 Jan 23.

Department of Paediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

Background: Although inborn errors of metabolism (IEM) are rare individually, collectively IEM cause substantial morbidity and mortality and the diagnosis is challenging.

Aims: To analyse epidemiological and clinical data, final diagnosis and clinical outcomes of patients with a suspected diagnosis of IEM (small molecule disorders type) admitted to a paediatric intensive care unit (PICU).

Methods: We collected and analysed medical records data of all patients admitted to the PICU at Alexandria University Children's Hospital, from January 2010 to December 2014, with a suspected or confirmed diagnosis of small molecule disorders, including clinical presentations, laboratory results and clinical outcomes. Read More

J Med Genet 2019 Mar 25;56(3):123-130. Epub 2019 Jan 25.

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

Primary genetic mitochondrial diseases are often difficult to diagnose, and the term 'possible' mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. Read More

Presse Med 2019 Feb 22;48(1 Pt 2):e77-e87. Epub 2019 Jan 22.

Department of Pediatrics, NU-Hospital Group, 45180 Uddevalla, Sweden; Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is a complex autoinflammatory disease with a clinical phenotype characterised by recurrent episodes of fever, systemic inflammation and symptoms and signs depicted in disease acronym. Although PFAPA is the most common autoinflammatory disease among children in many parts of the world, the condition is still an enigma, which include the regular episodes, the prompt responses to corticosteroids, the genetic bases for the familial clustering and therapeutic effects of tonsillectomy. This review explores PFAPA syndrome with the aim of describing the current clinical and scientific understanding of the condition. Read More

J Hum Genet 2019 Feb 25;64(2):65. Epub 2019 Jan 25.

Kumamoto University, Department of Pediatrics, Kumamoto, Japan.

Zhongguo Dang Dai Er Ke Za Zhi 2019 Jan;21(1):71-76

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou 510630, China.

GM1 gangliosidosis is an autosomal recessive disorder caused by galactosidase beta1 (GLB1) gene variants which affect the activity of β-galactosidase (GLB). GLB dysfunction causes abnormalities in the degradation of GM1 and its accumulation in lysosome. This article reports the clinical and genetic features of a child with GM1 gangliosidosis. Read More

Zhongguo Dang Dai Er Ke Za Zhi 2019 Jan;21(1):64-70

Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou 510632, China.

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder resulting from biallelic mutations of ABCC2 gene, with long-term or intermittent conjugated hyperbilirubinemia being the main clinical manifestation. This paper aims to report the clinical features and ABCC2 genotypes of an infant with DJS. A 9. Read More

J Hum Genet 2019 Apr 23;64(4):323-331. Epub 2019 Jan 23.

Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.

Metachromatic leukodystrophy due to Arylsulfatase A enzyme deficiency is an autosomal recessive disorder caused by biallelic variations in ARSA gene. Till date 186 variations have been reported in ARSA gene worldwide, but the variation spectrum in India is not known. The aim of this study was to identify the variation profile in Indian patients presenting with features of Arylsulfatase A deficient metachromatic leukodystrophy. Read More

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

Genetics and Genomic Medicine, UCL GOS Institute of Child Health, London, UK.

Vitamin B is present in our diet in many forms, however, only pyridoxal 5'-phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs nonphosphorylated B vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Read More

Am J Hum Genet 2019 Feb 17;104(2):287-298. Epub 2019 Jan 17.

Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA. Electronic address:

Hypusine is formed post-translationally from lysine and is found in a single cellular protein, eukaryotic translation initiation factor-5A (eIF5A), and its homolog eIF5A2. Biosynthesis of hypusine is a two-step reaction involving the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). eIF5A is highly conserved throughout eukaryotic evolution and plays a role in mRNA translation, cellular proliferation, cellular differentiation, and inflammation. Read More

J Hum Genet 2019 Apr 18;64(4):297-304. Epub 2019 Jan 18.

United Diagnostic and Research Center for Clinical Genetics, School of Public Health of Xiamen University & Xiamen Maternal and Child Health Hospital, Xiamen, Fujian, 361003, China.

COQ4 mutations have recently been shown to cause a broad spectrum of mitochondrial disorders in association with CoQ10 deficiency. Herein, we report the clinical phenotype, in silico and biochemical analyses, and intervention for a novel c.370 G > A (p. Read More

Biochim Biophys Acta Mol Basis Dis 2019 Jan 15. Epub 2019 Jan 15.

Departments of Clinical Chemistry, Pediatrics and Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology & Metabolism, 1105 AZ Amsterdam, the Netherlands. Electronic address:

Pyrimidine nucleotides are essential for a vast number of cellular processes and dysregulation of pyrimidine metabolism has been associated with a variety of clinical abnormalities. Inborn errors of pyrimidine metabolism affecting enzymes in the pyrimidine de novo and degradation pathway have been identified but no patients have been described with a deficiency in proteins affecting the cellular import of ribonucleosides. In this manuscript, we report the elucidation of the genetic basis of the observed uridine-cytidineuria in a patient presenting with fever, hepatosplenomegaly, persistent lactate acidosis, severely disturbed liver enzymes and ultimately multi-organ failure. Read More

J Hum Genet 2019 Apr 16;64(4):305-312. Epub 2019 Jan 16.

Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.

Cobalamin G (cblG) and cobalamin J (cblJ) defects are rare disorders of cbl metabolism caused by MTR and ABCD4 mutations, respectively. Patients with atypical biochemical features can be missed by current newborn screening using tandem mass spectrometry (MS/MS), in which total homocysteine (tHCY) in dried blood spots (DBS) is not a primary biomarker. Two Chinese patients suspected of cbl defect but missed by newborn screening were studied. Read More

BMC Gastroenterol 2019 Jan 11;19(1). Epub 2019 Jan 11.

Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.

Background: Hermansky-Pudlak syndrome (HPS) is a rare, genetically heterogeneous disorder that manifests oculocutaneous albinism together with bleeding diatheses that reflect a platelet storage pool deficiency. Ten genetic subtypes of this autosomal recessive condition have been described to date. Some patients with Hermansky-Pudlak syndrome type 1, 4, or 6 develop Crohn's-like inflammatory bowel disease at any age including early childhood, but most often in adolescence or young adulthood. Read More

Biochem Soc Trans 2019 02 9;47(1):149-155. Epub 2019 Jan 9.

Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine and Université de Montréal, Montréal, QC, Canada

Coenzyme A (CoA) thioesters (acyl-CoAs) are essential intermediates of metabolism. Inborn errors of acyl-CoA metabolism include a large fraction of the classical organic acidemias. These conditions can involve liver, muscle, heart and brain, and can be fatal. Read More

J Korean Med Sci 2019 Jan 26;34(1):e4. Epub 2018 Dec 26.

Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.

Background: Menkes disease (MD) is a rare X-linked hereditary multisystemic disorder that is caused by dysfunction of copper metabolism. Patients with MD typically present with progressive neurodegeneration, some connective tissue abnormalities, and characteristic "kinky" hair. In addition, various types of urological complications are frequent in MD because of underlying connective tissue abnormalities. Read More

Ann Clin Lab Sci 2018 Nov;48(6):785-789

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Mucolipidosis III alpha/beta (ML III alpha/beta) is an autosomal recessive lysosomal storage disorder caused by N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) deficiency. It is characterized by coarse facial features, developmental delay, short stature, and skeletal deformities. Its cardiovascular symptoms include valvular thickening or hypertrophic cardiomyopathy. Read More

Medicine (Baltimore) 2019 Jan;98(1):e14021

Institution of Pediatrics.

β-Ureidopropionase (βUP) deficiency is an autosomal recessive disease caused by abnormal changes in the pyrimidine-degradation pathway. This study aimed to investigate the mutation of β-ureidopropionase gene (UPB1) gene and clinical features of 7 Chinese patients with βUP deficiency.We reported 7 Chinese patients with βUP deficiency who were admitted at Tianjin Children's Hospital. Read More