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    Identification of ABC transporters acting in vitamin B12 metabolism in Caenorhabditis elegans.
    Mol Genet Metab 2017 Nov 11. 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 B12 (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 2017 Nov 10. Epub 2017 Nov 10.
    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 2017 Nov 3. Epub 2017 Nov 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 2017 Nov 1. 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.
    Introduction: 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. Case description: 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 2017 Oct 16. Epub 2017 Oct 16.
    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 2017 Oct 4. 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 2017 Oct 11. 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 (H2S). In this study, we assessed the role of CBS in H2S biogenesis.

    Results: We show that despite discouraging enzyme kinetics of alternative H2S-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 H2S. 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 Aug 16. 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 neonatal 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 B12 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 B12-trafficking proteins ABCD4 and LMBD1.
    J Biol Chem 2017 Jul 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 B12 (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 LMBRD1 and ABCD4 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 May 8. 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 Aug 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

    A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionine β-Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?
    Oxid Med Cell Longev 2017 22;2017:8940321. Epub 2017 Mar 22.
    CNR Institute of Molecular Biology and Pathology, Rome, Italy.
    The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5'-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood. Read More

    X-Linked Cobalamin Disorder (HCFC1) Mimicking Nonketotic Hyperglycinemia With Increased Both Cerebrospinal Fluid Glycine and Methylmalonic Acid.
    Pediatr Neurol 2017 Jun 7;71:65-69. Epub 2017 Jan 7.
    Department of Pediatrics, University of Colorado, School of Medicine, Aurora, Colorado. Electronic address:
    Background: Autosomal recessive or X-linked inborn errors of intracellular cobalamin metabolism can lead to methylmalonic aciduria and homocystinuria. In neonates, both increased cerebrospinal fluid glycine and cerebrospinal fluid/plasma glycine ratio are biochemical features of nonketotic hyperglycinemia.

    Methods: We describe a boy presenting in the neonatal period with hypotonia, tonic, clonic, and later myoclonic seizures, subsequently evolving into refractory epilepsy and severe neurocognitive impairment. Read More

    Combined methylmalonic acidemia and homocysteinemia presenting predominantly with late-onset diffuse lung disease: a case series of four patients.
    Orphanet J Rare Dis 2017 Mar 21;12(1):58. Epub 2017 Mar 21.
    Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, Nanlishi Road 56, Xicheng District, Beijing, People's Republic of China.
    Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities.We report 4 children with combined MMA and homocysteinemia who presented predominantly with late-onset diffuse lung diseases (DLD). Read More

    Cystathionine beta-synthase deficiency alters hepatic phospholipid and choline metabolism: Post-translational repression of phosphatidylethanolamine N-methyltransferase is a consequence rather than a cause of liver injury in homocystinuria.
    Mol Genet Metab 2017 Apr 2;120(4):325-336. Epub 2017 Mar 2.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address:
    Classical homocystinuria (HCU) due to inactivating mutation of cystathionine β-synthase (CBS) is a poorly understood life-threatening inborn error of sulfur metabolism. A previously described cbs-/- mouse model exhibits a semi-lethal phenotype due to neonatal liver failure. The transgenic HO mouse model of HCU exhibits only mild liver injury and recapitulates multiple aspects of the disease as it occurs in humans. Read More

    MANAGEMENT OF ENDOCRINE DISEASE: Diagnostic and therapeutic approach of tall stature.
    Eur J Endocrinol 2017 Jun 8;176(6):R339-R353. Epub 2017 Mar 8.
    Unidade de Endocrinologia GenéticaLaboratório de Endocrinologia Celular e Molecular (LIM/25), Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
    Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Read More

    Oxidative Stress in Homocystinuria Due to Cystathionine ß-Synthase Deficiency: Findings in Patients and in Animal Models.
    Cell Mol Neurobiol 2017 Mar 3. Epub 2017 Mar 3.
    Departamento de Análises, Faculdade de Farmácia, UFRGS, Avenida Ipiranga 2752, Porto Alegre, RS, 90610-000, Brazil.
    Homocystinuria is an inborn error of amino acid metabolism caused by deficiency of cystathionine ß-synthase (CBS) activity, biochemically characterized by homocysteine (Hcy) and methionine (Met) accumulation in biological fluids and high urinary excretion of homocystine. Clinical manifestations include thinning and lengthening of long bones, osteoporosis, dislocation of the ocular lens, thromboembolism, and mental retardation. Although the pathophysiology of this disease is poorly known, the present review summarizes the available experimental findings obtained from patients and animal models indicating that oxidative stress may contribute to the pathogenesis of homocystinuria. Read More

    Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report.
    BMC Neurol 2017 Feb 28;17(1):47. Epub 2017 Feb 28.
    Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan.
    Background: Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn error of metabolism inherited in autosomal recessive pattern and is associated with a wide spectrum of neurological abnormalities.

    Case Presentation: We herein describe a 15-year-old boy with MTHFR deficiency who presented with a slowly progressive decline of school performance and a spastic gait. Rapidly deteriorating psychosis and repetitive seizures triggered by a febrile infection prompted neurological investigation. Read More

    Cerebral venous thrombosis as the first presentation of classical homocystinuria in an adult patient.
    BMJ Case Rep 2017 Jan 30;2017. Epub 2017 Jan 30.
    Department of Endocrinology, University Hospital of Birmingham, Birmingham, UK.
    A 30-year-old woman presented with severe headache, dysarthria and right hemiparesis. She was treated for suspected viral encephalopathy and recovered over the following weeks although the headaches persisted. Two months later she was treated in-hospital for pulmonary embolism. Read More

    Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany.
    World J Pediatr 2017 Apr 15;13(2):136-143. Epub 2017 Jan 15.
    University of Heidelberg, Center for Pediatric and Adolescent Medicine, Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
    Background: Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-ß-synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar.

    Methods: A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Read More

    High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring.
    Hum Mol Genet 2017 Mar;26(5):888-900
    Departments of Human Genetics and Pediatrics, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
    Methylenetetrahydrofolate reductase (MTHFR) generates methyltetrahydrofolate for methylation reactions. Severe MTHFR deficiency results in homocystinuria and neurologic impairment. Mild MTHFR deficiency (677C > T polymorphism) increases risk for complex traits, including neuropsychiatric disorders. Read More

    Case 34-2016. A 17-Year-Old Boy with Myopia and Craniofacial and Skeletal Abnormalities.
    N Engl J Med 2016 11;375(19):1879-1890
    From the Departments of Pediatrics (D.A.S., A.E.L.), Oral and Maxillofacial Surgery (M.J.T.), and Radiology (S.J.W.), Massachusetts General Hospital, the Departments of Pediatrics (D.A.S., A.E.L.), Ophthalmology (T.C.C.), and Radiology (S.J.W.), Harvard Medical School, the Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine (M.J.T.), and the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (T.C.C.) - all in Boston.

    Simultaneous determination of plasma total homocysteine and methionine by liquid chromatography-tandem mass spectrometry.
    Clin Chim Acta 2017 Jan 12;464:93-97. Epub 2016 Nov 12.
    Division of Biochemical Genetics, Baylor Genetics, Houston, TX, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States. Electronic address:
    The sulfur-containing amino acid homocysteine is a cardiac risk factor and a biomarker for several inborn errors of metabolism in methionine synthesis. A simple LC-MS/MS method was developed and validated for determination of homocysteine and methionine in human plasma. Rapid separation was achieved using a reverse phase liquid chromatography. Read More

    N-Homocysteinylation impairs collagen cross-linking in cystathionine β-synthase-deficient mice: a novel mechanism of connective tissue abnormalities.
    FASEB J 2016 Nov 16;30(11):3810-3821. Epub 2016 Aug 16.
    Department of Biochemistry and Biotechnology, University of Life Sciences, Poznań, Poland;
    Cystathionine β-synthase (CBS) deficiency, a genetic disorder in homocysteine (Hcy) metabolism in humans, elevates plasma Hcy-thiolactone and leads to connective tissue abnormalities that affect the cardiovascular and skeletal systems. However, the underlying mechanism of these abnormalities is not understood. Hcy-thiolactone has the ability to form isopeptide bonds with protein lysine residues, which generates N-homocysteinylated protein. Read More

    Spectrum of ocular manifestations in cobalamin C and cobalamin A types of methylmalonic acidemia.
    Ophthalmic Genet 2016 Dec 15;37(4):404-414. Epub 2016 Mar 15.
    a Casey Eye Institute, Oregon Health & Science University , Portland , Oregon , USA.
    Background: Cobalamin C disease (cblC), which leads to methylmalonic acidemia with homocystinuria, is the most common inherited disorder of vitamin B12 metabolism. Reported ocular findings associated with cblC have been maculopathy, pigmentary retinopathy, and optic nerve atrophy. Cobalamin A disease (cblA) which causes an isolated methylmalonic acidemia without homocystinuria is rarer than cblC. Read More

    Functional characterization of missense mutations in severe methylenetetrahydrofolate reductase deficiency using a human expression system.
    J Inherit Metab Dis 2017 Mar 14;40(2):297-306. Epub 2016 Oct 14.
    Division of Metabolism, University Children's Hospital, CH-8032, Zurich, Switzerland.
    5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NADPH-dependent reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using FAD as the cofactor. Severe MTHFR deficiency is the most common inborn error of folate metabolism, resulting in hyperhomocysteinemia and homocystinuria. Approximately 70 missense mutations have been described that cause severe MTHFR deficiency, however, in most cases their mechanism of dysfunction remains unclear. Read More

    Peripheral nerve involvement in classic homocystinuria: an unusual association.
    BMJ Case Rep 2016 Sep 28;2016. Epub 2016 Sep 28.
    Department of Neurology, Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Portugal Institute of Physiology Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal.
    Classic homocystinuria is one of the most common causes of hereditary hyperhomocysteinemia. It is an autosomal recessive and multisystemic disorder due to cystathionine β-synthase deficiency. We described a case of an 18-year-old Portuguese man with an ischaemic stroke, who was subsequently diagnosed with classic homocystinuria [Thr191Met (c. Read More

    Targeted exome sequencing for the identification of complementation groups in methylmalonic aciduria: A south Indian experience.
    Clin Biochem 2017 Jan 31;50(1-2):68-72. Epub 2016 Aug 31.
    Sandor Life Sciences Pvt Ltd, Banjara Hills, Road No.3, Hyderabad, India.
    Objectives: In view of high incidence of methylmalonic aciduria (MMA) among South Indians, we have performed clinical, biochemical and molecular genetic evaluation of fifteen patients.

    Design And Methods: Targeted exome sequencing was performed for a panel of MMA causing genes i.e. Read More

    Cooccurrence of Postural Orthostatic Tachycardia Syndrome with Two Different Clinical Entities.
    Case Rep Pediatr 2016 19;2016:8542158. Epub 2016 Jun 19.
    Mehmet Akif Ersoy Training and Educational Hospital, Department of Pediatrics, 34303 Istanbul, Turkey.
    Postural orthostatic tachycardia syndrome (POTS) is an abnormal heart rate response to a positional change. Several potential mechanisms for pathophysiology of POTS are defined. This syndrome can coexist with different clinical situations. Read More

    Determination of CSF 5-methyltetrahydrofolate in children and its application for defects of folate transport and metabolism.
    Clin Chim Acta 2016 Sep 27;460:120-5. Epub 2016 Jun 27.
    Department of Child Neurology, Okayama University Hospital, Okayama, Japan; Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
    Objective: To describe an assay of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF) of children, to determine reference values, and to report the clinical significance of this assay in metabolic disorders affecting folate transport and metabolism.

    Methods: CSF 5MTHF was determined by high-performance liquid chromatography with fluorescent detection in pediatric patients including one with FOLR1 gene mutation and one with methylenetetrahydrofolate reductase (MTHFR) deficiency. CSF total folate was measured using an automated analyzer. Read More

    A Case of Homocystinuria Misdiagnosed as Moyamoya Disease: A Case Report.
    Iran Red Crescent Med J 2016 Apr 9;18(4):e30332. Epub 2016 Mar 9.
    Department of Pediatrics, Bagcilar Training and Research Hospital, Istanbul, Turkey.
    Introduction: Homocystinuria is a hereditary disease caused by a defect in the enzymes involved in metabolizing methionine. Homocystinuria can influence many systems and may be mistaken for other diseases, including Moyamoya disease. Here, we report the case of a 10-year-old male patient with a diagnosis of Moyamoya disease who had been monitored for that for an extended period. Read More

    Newborn Screening for Vitamin B6 Non-responsive Classical Homocystinuria: Systematical Evaluation of a Two-Tier Strategy.
    JIMD Rep 2017 21;32:87-94. Epub 2016 Jun 21.
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
    Background: In classical homocystinuria (HCU, MIM# 236200) due to the deficiency of cystathionine β-synthase (EC 4.2.1. Read More

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