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    2126 results match your criteria Homocystinuria

    1 OF 43

    Whole-exome Sequencing Helps the Diagnosis and Treatment in Children with Neurodevelopmental Delay Accompanied Unexplained Dyspnea.
    Sci Rep 2018 Mar 26;8(1):5214. Epub 2018 Mar 26.
    Pediatric Intensive Care Unit, Anhui Provincial Children's Hospital, Hefei, 230029, P.R. China.
    Neurodevelopmental delay accompanied unexplained dyspnea is a highly lethal disease in clinic. This study is to investigate the performance characteristics of trio whole exome sequencing (Trio-WES) in a pediatric setting by presenting our patient cohort and displaying the diagnostic yield. A total of 31 pediatric patients showing neurodevelopmental delay accompanied unexplained dyspnea were admitted to our hospital and referred for molecular genetic testing using Trio-WES. Read More

    Homocysteine and Hyperhomocysteinaemia.
    Curr Med Chem 2018 Mar 12. Epub 2018 Mar 12.
    Institute of nuclear science Vinca, University of Belgrade, Laboratory of Radiobiology and Molecular Genetics, Belgrade. Serbia.
    Homocysteine (Hcy) is thiol group containing the amino acid, which naturally occurs in all humans. Hcy is degraded in the body through two metabolic pathways, while a minor part is excreted through kidneys. The chemical reactions that are necessary for degradation of Hcy require the presence of the folic acid, vitamins B6 and B12. Read More

    Pharmacokinetics and pharmacodynamics of PEGylated truncated human cystathionine beta-synthase for treatment of homocystinuria.
    Life Sci 2018 May 9;200:15-25. Epub 2018 Mar 9.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address:
    Aims: PEGylated human truncated cystathionine beta-synthase, lacking the C-terminal regulatory domain (PEG-CBS), is a promising preclinical candidate for enzyme replacement therapy in homocystinuria (HCU). It was designed to function as a metabolic sink to decrease the severely elevated plasma and tissue homocysteine concentrations. In this communication, we evaluated pharmacokinetics (PK), pharmacodynamics (PD) and sub-chronic toxicity of PEG-CBS in homocystinuric mice, wild type rats and monkeys to estimate the minimum human efficacious dose for clinical trials. Read More

    Case 7-2018: A 25-Year-Old Man with New-Onset Seizures.
    N Engl J Med 2018 Mar;378(10):941-948
    From the Departments of Neurology (E.C.C.), Radiology (S.Y.H.), Genetics (A.K.), and Pathology (M.W.R.), Massachusetts General Hospital, and the Departments of Neurology (E.C.C.), Radiology (S.Y.H.), Genetics (A.K.), and Pathology (M.W.R.), Harvard Medical School - both in Boston.

    Eight novel mutations of CBS gene in nine Chinese patients with classical homocystinuria.
    World J Pediatr 2018 Mar 5. Epub 2018 Mar 5.
    Department of Pediatrics, Peking University First Hospital, No. 1 Xi'anmen Street, West District, Beijing, 100034, China.
    Background: Classical homocystinuria (homocysteinemia type 1, MIM# 236200) is a rare inherited disorder in Mainland China. This study aimed to identify mutations in the cystathionine β-synthase (CBS) gene which are associated with classical homocystinuria in nine Chinese patients.

    Methods: Nine Chinese patients were diagnosed at the age of 5 years 4 months to 18 years by plasma total homocysteine and blood methionine determination. Read More

    Inborn Errors of Metabolism with Cognitive Impairment: Metabolism Defects of Phenylalanine, Homocysteine and Methionine, Purine and Pyrimidine, and Creatine.
    Pediatr Clin North Am 2018 Apr;65(2):267-277
    Division of Medical Genetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address:
    Phenylketonuria is a defect in phenylalanine metabolism resulting in the excretion of phenylketones and severe intellectual disability. The principle of eliminating the offending amino acid from the diet as a successful treatment strategy was demonstrated. The development of a low methionine diet to treat homocystinuria was established after identifying the transsulfuration pathway resulting in cysteine synthesis. Read More

    Poorly Controlled Homocystinuria: A Rare Cause of Ischemic Priapism?
    Sex Med 2018 Feb 17. Epub 2018 Feb 17.
    Andrology Department, University College London Hospital, London, UK.
    We report on the 1st case of ischemic priapism secondary to poorly controlled homocystinuria. Homocystinuria is a rare, autosomal recessive, inherited disorder of metabolism that is caused by a deficiency of cystathionine synthase, leading to marked hyperhomocysteinemia. Arterial and/or venous thromboemboli are a major cause of mortality and morbidity in patients with homocystinuria. Read More

    Enzyme Replacement Therapy Ameliorates Multiple Symptoms of Murine Homocystinuria.
    Mol Ther 2018 Mar 19;26(3):834-844. Epub 2017 Dec 19.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address:
    Classical homocystinuria (HCU) is the most common inherited disorder of sulfur amino acid metabolism caused by deficiency in cystathionine beta-synthase (CBS) activity and characterized by severe elevation of homocysteine in blood and tissues. Treatment with dietary methionine restriction is not optimal, and poor compliance leads to serious complications. We developed an enzyme replacement therapy (ERT) and studied its efficacy in a severe form of HCU in mouse (the I278T model). Read More

    Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations.
    Metab Brain Dis 2018 Jan 26. Epub 2018 Jan 26.
    Department of Neurology, Qilu Hospital, Shandong University, 107#,Wen Hua Xi Road, Ji'nan, 250012, People's Republic of China.
    The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. Read More

    Hyperhomocysteinemia and Risk of First Venous Thrombosis: The Influence of (Unmeasured) Confounding Factors.
    Am J Epidemiol 2018 Jan 12. Epub 2018 Jan 12.
    Meta-analyses have reported a 2-3 fold increased risk of venous thrombosis (VT) in individuals with hyperhomocysteinemia, however, confounding factors were generally not considered. In contrast, randomized trials of homocysteine-lowering therapy and VT risk were negative. We investigated if hyperhomocysteinemia is associated with VT in the MEGA case-control study (1999-2004) from the Netherlands (1,689 cases and 1,726 controls), taking into account measured and unmeasured confounders. Read More

    CBS mutations are good predictors for B6-responsiveness: A study based on the analysis of 35 Brazilian Classical Homocystinuria patients.
    Mol Genet Genomic Med 2018 Mar 20;6(2):160-170. Epub 2018 Jan 20.
    Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
    Background: Classical homocystinuria (HCU) is a monogenic disease caused by the deficient activity of cystathionine β-synthase (CβS). The objective of this study was to identify the CBS mutations in Brazilian patients with HCU.

    Methods: gDNA samples were obtained for 35 patients (30 families) with biochemically confirmed diagnosis of HCU. Read More

    Symmetrical Drug-related Intertriginous and Flexural Exanthema Induced by Doxycycline.
    Cureus 2017 Nov 10;9(11):e1836. Epub 2017 Nov 10.
    Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School.
    Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by erythema over the buttocks, thighs, groin, and flexural regions most commonly associated with the use of beta-lactam antibiotics. Although the exact pathophysiology of this disease remains unknown, it is theorized to be the result of a delayed hypersensitivity response presenting as a cutaneous eruption days to weeks after exposure to the drug. The treatment involves discontinuation of the suspected medication, symptomatic control of pruritus, and topical steroid therapy. Read More

    Homocystinuria due to cystathionine beta-synthase (CBS) deficiency in Russia: Molecular and clinical characterization.
    Mol Genet Metab Rep 2018 Mar 27;14:47-54. Epub 2017 Dec 27.
    Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russia.
    We present the results of the 45-year clinical observation of 27 Russian homocystinuria patients. We made a mutation analysis of the gene for thirteen patients from eleven unrelated genealogies. All patients except for the two were compound heterozygotes for the mutations detected. Read More

    Atypical adult-onset methylmalonic acidemia and homocystinuria presenting as hemolytic uremic syndrome.
    CEN Case Rep 2018 May 2;7(1):73-76. Epub 2018 Jan 2.
    Nephrology Department, Centro Hospitalar de Lisboa Central E.P.E., Hospital Curry Cabral, Rua da Beneficência 8, 1069-166, Lisbon, Portugal.
    Thrombotic microangiopathy (TMA) syndromes can be secondary to a multitude of different diseases. Most can be identified with a systematic approach and, when excluded, TMA is generally attributed to a dysregulation in the activity of the complement alternative pathways-atypical hemolytic uremic syndrome (aHUS). We present a challenging case of a 19-year-old woman who presented with thrombotic microangiopathy, which was found to be caused by methylmalonic acidemia and homocystinuria, a rare vitamin B12 metabolism deficiency. Read More

    Homocystinuria with Stroke and Positive Familial History.
    Adv Biomed Res 2017 25;6:132. Epub 2017 Oct 25.
    Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
    Homocystinuria is the second most common treatable aminoacidopathy. Clinically, affected patients present with eye, skeleton, central nervous system, and most importantly, vascular system abnormalities. This autosomal recessive disorder leads to accumulation of homocysteine and its metabolites in the blood and urine. Read More

    Crystal structure of cystathionine β-synthase from honeybee Apis mellifera.
    J Struct Biol 2018 Apr 21;202(1):82-93. Epub 2017 Dec 21.
    Structural Biology Unit, Center for Cooperative Research in Biosciences (CIC Biogune), Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain. Electronic address:
    Cystathionine β-synthase (CBS), the key enzyme in the transsulfuration pathway, links methionine metabolism to the biosynthesis of cellular redox controlling molecules. CBS catalyzes the pyridoxal-5'-phosphate-dependent condensation of serine and homocysteine to form cystathionine, which is subsequently converted into cysteine. Besides maintaining cellular sulfur amino acid homeostasis, CBS also catalyzes multiple hydrogen sulfide-generating reactions using cysteine and homocysteine as substrates. Read More

    Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake.
    J Nutr Metab 2017 15;2017:8570469. Epub 2017 Nov 15.
    National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland.
    A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU). There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels. Read More

    Identification of ABC transporters acting in vitamin B metabolism in Caenorhabditis elegans.
    Mol Genet Metab 2017 Dec 11;122(4):160-171. Epub 2017 Nov 11.
    Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, T2N 4N1, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, T2N 4N1, Canada. Electronic address:
    Vitamin B (cobalamin, Cbl) is a micronutrient essential to human health. Cbl is not utilized as is but must go through complex subcellular and metabolic processing to generate two cofactor forms: methyl-Cbl for methionine synthase, a cytosolic enzyme; and adenosyl-Cbl for methylmalonyl-CoA mutase, a mitochondrial enzyme. Some 10-12 human genes have been identified responsible for the intracellular conversion of Cbl to cofactor forms, including genes that code for ATP-binding cassette (ABC) transporters acting at the lysosomal and plasma membranes. Read More

    Potential Pharmacological Chaperones for Cystathionine Beta-Synthase-Deficient Homocystinuria.
    Handb Exp Pharmacol 2018 ;245:345-383
    Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, USA.
    Classical homocystinuria (HCU) is the most common loss-of-function inborn error of sulfur amino acid metabolism. HCU is caused by a deficiency in enzymatic degradation of homocysteine, a toxic intermediate of methionine transformation to cysteine, chiefly due to missense mutations in the cystathionine beta-synthase (CBS) gene. As with many other inherited disorders, the pathogenic mutations do not target key catalytic residues, but rather introduce structural perturbations leading to an enhanced tendency of the mutant CBS to misfold and either to form nonfunctional aggregates or to undergo proteasome-dependent degradation. Read More

    Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism.
    FASEB J 2018 Mar 3;32(3):1265-1280. Epub 2018 Jan 3.
    Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, Colorado, USA.
    Cystathionine β-synthase-deficient homocystinuria (HCU) is a poorly understood, life-threatening inborn error of sulfur metabolism. Analysis of hepatic glutathione (GSH) metabolism in a mouse model of HCU demonstrated significant depletion of cysteine, GSH, and GSH disulfide independent of the block in trans-sulfuration compared with wild-type controls. HCU induced the expression of the catalytic and regulatory subunits of γ-glutamyl ligase, GSH synthase (GS), γ-glutamyl transpeptidase 1, 5-oxoprolinase (OPLAH), and the GSH-dependent methylglyoxal detoxification enzyme, glyoxalase-1. Read More

    Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options.
    Biochem Genet 2018 Apr 1;56(1-2):7-21. Epub 2017 Nov 1.
    DHQ Hospital, Faisalabad Medical University, Faisalabad, Pakistan.
    Inborn errors of metabolism (IEMs) are a group of inherited metabolic disorders which are caused by mutations in the specific genes that lead to impaired proteins or enzymes production. Different metabolic pathways are perturbed due to the deficiency or lack of enzymes. To date, more than 500 IEMs have been reported with most of them being untreatable. Read More

    Bilateral posterior crystalline lens dislocations in an otherwise healthy child.
    GMS Ophthalmol Cases 2017 20;7:Doc26. Epub 2017 Oct 20.
    King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, National Guard Hospital, Jeddah, Saudi Arabia.
    Ectopia lentis is defined as a crystalline lens displacement, either partially or completely, due to zonular abnormalities. It can be a result of trauma, hereditary ocular disease, or part of systemic diseases, like Marfan syndrome and homocystinuria. We report a case of a medically free 16-year-old girl, who was referred to our hospital complaining of poor vision and a squint in both eyes since childhood. Read More

    Enzyme replacement therapy prevents loss of bone and fat mass in murine homocystinuria.
    Hum Mutat 2018 Feb 13;39(2):210-218. Epub 2017 Nov 13.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
    Skeletal and connective tissue defects are the most striking symptoms in patients suffering from classical homocystinuria (HCU). Here, we determined body composition and bone mass in three mouse models of HCU and assessed whether a long-term administration of enzyme replacement therapy (ERT) corrected the phenotype. The mouse models of HCU were analyzed using dual-energy X-ray absorptiometry and the data were complemented by plasma biochemical profiles. Read More

    Diagnosis of cobalamin C deficiency with renal abnormality from onset in a Chinese child by next generation sequencing: A case report.
    Exp Ther Med 2017 Oct 18;14(4):3637-3643. Epub 2017 Aug 18.
    Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.
    The aim of the present study was to present the diagnosis and treatment course of a patient with cobalamin C deficiency (cblC) hospitalized with renal function abnormality from the onset. A female, 7-year-old patient who presented with a cough and progressive dyspnea for 1 day was admitted to the Children's Hospital of Nanjing Medical University (Nanjing, China). A routine clinical examination was performed, including physical examination, routine blood and urine tests, blood gas analysis, computed tomography scans of the head, chest and abdomen, electrocardiogram, echocardiography and abdominal ultrasonography. Read More

    Isolated aortic root dilation in homocystinuria.
    J Inherit Metab Dis 2018 Jan 4;41(1):109-115. Epub 2017 Oct 4.
    Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Background: Vascular complications in homocystinuria have been known for many years, but there have been no reports to date on involvement of the ascending aorta.

    Methods: We conducted a cross-sectional study of patients with homocystinuria, known to a single metabolic centre, and evaluated in 2016 with a transthoracic echocardiogram. Aortic root dilation was defined as Z-score ≥ 2. Read More

    Homocystinuria with Cerebral Venous Sinus Thrombosis: Excellent Recovery with Intravenous Recombinant Tissue Plasminogen Activator.
    Iran J Child Neurol 2017 ;11(3):48-52
    Department of Pediatrics, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India.
    Hyperhomocysteinemia can cause cerebral venous thrombosis. Recombinant tissue plasminogen activator is one of the treatment options for cerebral venous thrombosis in selected cases. We present here a 7-year-old boy with homocysteinuria with stroke. Read More

    Quantitative Assessment of Microstructural Changes of the Retina in Infants With Congenital Zika Syndrome.
    JAMA Ophthalmol 2017 Oct;135(10):1069-1076
    Department of Ophthalmology, Federal University of São Paulo, Paulista Medical School, São Paulo, Brazil.
    Importance: A better pathophysiologic understanding of the neurodevelopmental abnormalities observed in neonates exposed in utero to Zika virus (ZIKV) is needed to develop treatments. The retina as an extension of the diencephalon accessible to in vivo microcopy with spectral-domain optical coherence tomography (SD-OCT) can provide an insight into the pathophysiology of congenital Zika syndrome (CZS).

    Objective: To quantify the microstructural changes of the retina in CZS and compare these changes with those of cobalamin C (cblC) deficiency, a disease with potential retinal maldevelopment. Read More

    Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase.
    Antioxid Redox Signal 2018 02 11;28(4):311-323. Epub 2017 Oct 11.
    1 Department of Pediatrics, University of Colorado , School of Medicine, Aurora, Colorado.
    Aims: The transsulfuration pathway enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase are thought to be the major source of hydrogen sulfide (HS). In this study, we assessed the role of CBS in HS biogenesis.

    Results: We show that despite discouraging enzyme kinetics of alternative HS-producing reactions utilizing cysteine compared with the canonical condensation of serine and homocysteine, our simulations of substrate competitions at biologically relevant conditions suggest that cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of HS. Read More

    Cerebral venous sinus thrombosis in homocystinuria: Dietary intervention in conjunction with anticoagulation.
    SAGE Open Med Case Rep 2017 1;5:2050313X17722289. Epub 2017 Aug 1.
    Department of Neurology, Beaumont Hospital, Dublin, UK.
    The presentation of cerebral venous sinus thrombosis may be acute or chronic with a progressive clinical course. The diagnosis can be challenging, and there are several clinical syndromes associated with the disease. It is also an uncommon but recognised complication of homocystinuria. Read More

    Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria.
    FASEB J 2017 12 16;31(12):5495-5506. Epub 2017 Aug 16.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA;
    Classical homocystinuria (HCU) is an inborn error of sulfur amino acid metabolism caused by deficient activity of cystathionine β-synthase (CBS), resulting in an accumulation of homocysteine and a concomitant decrease of cystathionine and cysteine in blood and tissues. In mice, the complete lack of CBS is neonatally lethal. In this study, newborn CBS-knockout (KO) mice were treated with recombinant polyethyleneglycolylated human truncated CBS (PEG-CBS). Read More

    Leptin concentrations and SCD-1 indices in classical homocystinuria: Evidence for the role of sulfur amino acids in the regulation of lipid metabolism.
    Clin Chim Acta 2017 Oct 8;473:82-88. Epub 2017 Aug 8.
    Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; BRAIN Laboratory (Basic Research and Advanced Investigations in Neurosciences) - Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Electronic address:
    Background: We describe body composition, lipid metabolism and Stearoyl-CoA desaturase-1 (SCD-1) indices in patients with classical homocystinuria (HCU).

    Methods: Eleven treated HCU patients and 16 healthy controls were included. Body composition and bone mineral density were assessed by dual X-ray absorptiometry. Read More

    Adult classical homocystinuria requiring parenteral nutrition: Pitfalls and management.
    Clin Nutr 2017 Jul 25. Epub 2017 Jul 25.
    Service of Adult Intensive Care and Burns Centre, Lausanne University Hospital, Lausanne, Switzerland.
    Background: Homocystinuria due to cystathionine beta synthase (CBS) deficiency presents with a wide clinical spectrum. Treatment by the enteral route aims at reducing homocysteine levels by using vitamin B6, possibly methionine-restricted diet, betaine and/or folate and vitamin B supplementation. Currently no nutritional guidelines exist regarding parenteral nutrition (PN) under acute conditions. Read More

    Spinal cord injury following a mild trauma in homocystinuria-related bone frailty: neurorehabilitation and education on bone health management.
    Int J Rehabil Res 2017 Dec;40(4):374-376
    aDepartment of Physical Medicine & Rehabilitation, Hamad Medical Corporation, Doha, Qatar bDepartment of Physical Medicine and Rehabilitation, Scientific Institute of Lissone, IRCCS, Istituti Clinici Scientifici Maugeri, Lissone MB, Italy.
    Homocystinuria (HCU) is a rare autosomal recessive disease characterized by the deficiency of cystathionine β-synthetase, presenting with variable clinical features including micronutrient deficiency-related osteoporosis. Early-onset osteoporosis results in increased bone fragility, which is associated with low-impact fractures. To date, no traumatic myelopathy has ever been described in patients with HCU. Read More

    Homocystinuria (HC) and Neurofibromatosis Type-1 (NF-1): An Unusual Presentation in a Child.
    J Coll Physicians Surg Pak 2016 Nov;26(11):140-141
    Department of Ophthalmology, Armed Forces Institute of Ophthalmology, Military Hospital, Rawalpindi.
    Homocystinuria (HC) and neurofibromatosis type-1 (NF-1) are two genetically determined conditions with variable clinical manifestations. HC is a neurocutaneous autosomal recessive condition while NF-1 is an autosomal dominant phacomatosis. Both HC and NF-1 present with distinct systemic as well as ocular manifestations; however, vascular complications can occur in both the conditions. Read More

    Cystathionine β-synthase deficiency: Of mice and men.
    Mol Genet Metab 2017 Jul 19;121(3):199-205. Epub 2017 May 19.
    Cancer Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. Electronic address:
    Cystathionine β-synthase (CBS) deficiency (Online Mendelian Inheritance in Man [OMIM] 236,200) is an autosomal recessive disorder that is caused by mutations in the CBS gene. It is the most common inborn error of sulfur metabolism and is the cause of classical homocystinuria, a condition characterized by very high levels of plasma total homocysteine and methionine. Although recognized as an inborn error of metabolism over 60years ago, these is still much we do not understand related to how this specific metabolic defect gives rise to its distinct phenotypes. Read More

    Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B-trafficking proteins ABCD4 and LMBD1.
    J Biol Chem 2017 07 1;292(28):11980-11991. Epub 2017 Jun 1.
    From the Division of Metabolism and Children's Research Center, University Children's Hospital, CH-8032 Zurich, Switzerland,
    Vitamin B (cobalamin (Cbl)), in the cofactor forms methyl-Cbl and adenosyl-Cbl, is required for the function of the essential enzymes methionine synthase and methylmalonyl-CoA mutase, respectively. Cbl enters mammalian cells by receptor-mediated endocytosis of protein-bound Cbl followed by lysosomal export of free Cbl to the cytosol and further processing to these cofactor forms. The integral membrane proteins LMBD1 and ABCD4 are required for lysosomal release of Cbl, and mutations in the genes and result in the cobalamin metabolism disorders cblF and cblJ. Read More

    The c.797 G>A (p.R266K) cystathionine β-synthase mutation causes homocystinuria by affecting protein stability.
    Hum Mutat 2017 Jul 22;38(7):863-869. Epub 2017 May 22.
    Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
    Mutations in the cystathionine beta-synthase (CBS) gene are the cause of classical homocystinuria, the most common inborn error in sulfur metabolism. The c.797 G>A (p. Read More

    Optical coherence tomography morphology and evolution in cblC disease-related maculopathy in a case series of very young patients.
    Acta Ophthalmol 2017 Dec 8;95(8):e776-e782. Epub 2017 May 8.
    Pediatric Ophthalmology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
    Purpose: To describe the retinal structure of a group of patients affected by methylmalonic aciduria with homocystinuria cblC type, caused by mutations in the MMACHC gene, using spectral domain optical coherence tomography (SD-OCT).

    Methods: Young patients (n = 11, age 0-74 months) with cblC disease, detected by newborn screening or clinically diagnosed within 40 days of life, underwent molecular analysis and complete ophthalmic examination, including fundus photography and SD-OCT. In one case, we also performed fluorescein angiography (FA) and standard electroretinography (ERG). Read More

    Newborn screening by matrix-assisted laser desorption/ionization mass spectrometry based on parylene-matrix chip.
    Anal Biochem 2017 08 29;530:31-39. Epub 2017 Apr 29.
    Department of Materials Sciences and Engineering, Yonsei University, Seoul, South Korea. Electronic address:
    Newborn screening for diagnosis of phenylketonuria, homocystinuria, and maple syrup urine disease have been conducted by analyzing the concentration of target amino acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) based on parylene-matrix chip. Parylene-matrix chip was applied to MALDI-ToF MS analysis reducing the matrix peaks significantly at low mass-to-charge ratio range (m/z < 500). Reproducibility of inter-spot and intra-spot analyses of amino acids was less than 10%. Read More

    Engineering and Characterization of an Enzyme Replacement Therapy for Classical Homocystinuria.
    Biomacromolecules 2017 Jun 1;18(6):1747-1761. Epub 2017 May 1.
    Department of Pediatrics, University of Colorado School of Medicine , Aurora, Colorado 80045, United States.
    Homocystinuria due to loss of cystathionine beta-synthase (CBS) causes accumulation of homocysteine and depletion of cysteine. Current treatments are suboptimal, and thus the development of an enzyme replacement therapy based on PEGylated human truncated CBS (PEG-CBS) has been initiated. Attenuation of potency was observed, which necessitated a screen of several PEG-CBS conjugates for their efficacy to correct and maintain the plasma metabolite profile of murine homocystinuria after repeated administrations interrupted with washouts. Read More

    [Our experience in the diagnosis and treatment of postural orthostatic tachycardia syndrome, vasovagal syncope, and inappropriate sinus tachycardia in children].
    Turk Kardiyol Dern Ars 2017 Apr;45(3):227-234
    Department of Pediatric Cardiology, Istanbul University Cerrahpaşa Medical Faculty, Istanbul, Turkey.
    Objectives: The aim of this study was to share our experience in the diagnosis and treatment of patients who presented at our clinic with syncope, pre-syncope, dizziness, and palpitations.

    Study Design: Patients who were treated at pediatric cardiology clinic for complaints of syncope, dizziness, and palpitations between 2014 and 2016 were enrolled in the study. Detailed history of the patients, physical examination findings, laboratory and electrocardiogram results were recorded. Read More

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