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    2062 results match your criteria Homocystinuria

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    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 Jan 19. Epub 2017 Jan 19.
    Center for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
    Background: Newborn screening is a precondition for early diagnosis and succeßsful treatment of remethylation disorders and classical homocystinuria (cystathionine-β-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 Jan 9. Epub 2017 Jan 9.
    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

    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 2016 Jun 21. 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

    [Peripheral artery disease in patients younger than 50 years old: Which etiology?].
    Ann Cardiol Angeiol (Paris) 2016 Sep 16;65(4):275-85. Epub 2016 Jun 16.
    Imagerie cœur-vaisseaux, centre hospitalier universitaire, hôpital Pontchaillou, 2, rue Henri-Le-Guilloux, 35033 Rennes, France; Université de Rennes 1, Inserm, centre d'investigation clinique CIC 1414, 35033 Rennes, France. Electronic address:
    Peripheral arterial disease (PAD) encompasses disease of all arteries of the body except the coronary arteries. The main etiology whatever the patient's age is atherosclerosis. Different etiologies can induce PAD especially when patients are younger than 50 years old and have no cardiovascular risk factors (smoking, hypertension, diabetes…). Read More

    Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity.
    Pediatr Nephrol 2016 Jun 11. Epub 2016 Jun 11.
    Division of Paediatric Nephrology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
    Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B12) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia, hypotonia) and variable extracentral nervous system involvement (failure to thrive, cardiovascular, renal, ocular) manifesting predominantly early in life, sometimes during gestation. To enhance awareness and understanding of renal disease associated with cblC defect, we studied biochemical, genetic, clinical, and histopathological data from 36 patients. Read More

    Ocular Pseudoexfoliation Syndrome Linkage to Cardiovascular Disease.
    Curr Cardiol Rep 2016 Jul;18(7):61
    Department of Surgery, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, 77030, USA.
    Purpose Of Review: Pseudoexfoliation syndrome (PEX) is a common cause of open-angle glaucoma that is characterized by stress-induced elastic microfibrillopathy related to an accumulation of matrix metalloproteinases. The accumulation of matrix metalloproteinases increases deposition of protein substance within ocular structures and other organs including the heart. Many studies have associated the presence of cardiovascular disease with pseudoexfoliation syndrome, but much debate exists between studies in terms of significant relationships. Read More

    Enzyme replacement with PEGylated cystathionine β-synthase ameliorates homocystinuria in murine model.
    J Clin Invest 2016 Jun 16;126(6):2372-84. Epub 2016 May 16.
    Homocystinuria, which typically results from cystathionine β-synthase (CBS) deficiency, is the most common defect of sulfur amino acid metabolism. CBS condenses homocysteine and serine to cystathionine that is then converted to cysteine. Individuals with homocystinuria have markedly elevated plasma levels of homocysteine and methionine and reduced concentrations of cystathionine and cysteine. Read More

    Vision of correction for classic homocystinuria.
    J Clin Invest 2016 Jun 16;126(6):2043-4. Epub 2016 May 16.
    Inherited metabolic disorders are often characterized by the lack of an essential enzyme and are currently treated by dietary restriction and other strategies to replace the substrates or products of the missing enzyme. Patients with homocystinuria lack the enzyme cystathionine β-synthase (CBS), and many of these individuals do not respond to current treatment protocols. In this issue of the JCI, Bublil and colleagues demonstrate that enzyme replacement therapy (ERT) provides long-term amelioration of homocystinuria-associated phenotypes in CBS-deficient murine models. Read More

    The remarkable S. Harvey Mudd - A reminiscence.
    Mol Genet Metab 2016 Jul 27;118(3):143-4. Epub 2016 Apr 27.
    Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. Electronic address:
    Harvey Mudd was the father of methionine metabolic disorders. Beginning with his identification of the enzyme defect in homocystinuria, he co-discovered cobalamin C disorder as the first known human disorder of vitamin B12 metabolism, thereby extending our concept of homocystinuria as a key feature of related disorders rather than a single disease, and identified new disorders that produce hypermethioninemia. He had no equal in our understanding of how critical methionine metabolism is to human homeostasis. Read More

    MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature.
    J Genet Couns 2016 Oct 30;25(5):901-11. Epub 2016 Apr 30.
    Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, OH, USA.
    The 5, 10 methylenetetrahydrofolate reductase (MTHFR) enzyme is a catalyst in the folate metabolism pathway, the byproducts of which are involved in the remethylation of homocysteine to methionine. Methionine is a precursor for a major DNA methyl donor and is important for DNA methylation and gene regulation. Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria. Read More

    Homocystinuria: Therapeutic approach.
    Clin Chim Acta 2016 Jul 6;458:55-62. Epub 2016 Apr 6.
    Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110 007, India. Electronic address:
    Homocystinuria is a disorder of sulfur metabolism pathway caused by deficiency of cystathionine β-synthase (CBS). It is characterized by increased accumulation of homocysteine (Hcy) in the cells and plasma. Increased homocysteine results in various vascular and neurological complications. Read More

    Quantitative Analysis of Total Plasma Homocysteine by LC-MS/MS.
    Curr Protoc Hum Genet 2016 Apr 1;89:17.21.1-17.21.10. Epub 2016 Apr 1.
    Department of Genetics, University of Alabama-Birmingham School of Medicine, Birmingham, Alabama.
    Homocysteine is a nonessential, sulfur-containing amino acid involved in one-carbon (folate) metabolism. A number of inherited and acquired conditions cause increased accumulation of this metabolite in blood (homocysteinemia) and other biofluids. Homocysteinemia is a risk factor for cardiovascular disease, including recurrent thrombosis. Read More

    Endoplasmic Reticulum Stress and Autophagy in Homocystinuria Patients with Remethylation Defects.
    PLoS One 2016 9;11(3):e0150357. Epub 2016 Mar 9.
    Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular-SO UAM-CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, 28049 Madrid / Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, IDIPaz, Spain.
    Proper function of endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site as well as perturbation of mitochondria-associated ER membranes (MAMs) have been linked to neurodegenerative and metabolic diseases. Previously, we have observed an increase in ROS and apoptosis levels in patient-derived fibroblasts with remethylation disorders causing homocystinuria. Here we show increased mRNA and protein levels of Herp, Grp78, IP3R1, pPERK, ATF4, CHOP, asparagine synthase and GADD45 in patient-derived fibroblasts suggesting ER stress and calcium perturbations in homocystinuria. Read More

    Targeting Cystathionine Beta-Synthase Misfolding in Homocystinuria by Small Ligands: State of the Art and Future Directions.
    Curr Drug Targets 2016 ;17(13):1455-70
    Department of Pediatrics, School of Medicine, University of Colorado, 12800 E 19th Ave, Mail Stop 8313, Aurora, CO, 80045, USA.
    Classical homocystinuria (HCU) is the most common loss-of-function inborn error of sulfur amino acids 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 betasynthase (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 non-functional aggregates or to undergo proteasome-dependent degradation. Read More

    Ocular manifestations of genetic skin disorders.
    Clin Dermatol 2016 Mar-Apr;34(2):242-75. Epub 2015 Dec 2.
    The Vision Center, Children's Hospital Los Angeles; Department of Ophthalmology, Keck School of Medicine, University of Southern California, 4650 Sunset Blvd, MS #88, Los Angeles, CA, 90027.
    Genetic skin diseases, or genodermatoses, often have extracutaneous manifestations. Ocular manifestations in particular can have significant clinical implications, like blindness. Other manifestations, such as the corneal opacities that occur in X-linked ichthyosis, are asymptomatic but characteristic of a particular genodermatosis. Read More

    Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency.
    Hum Mutat 2016 May 18;37(5):427-38. Epub 2016 Mar 18.
    Division of Metabolism and Children's Research Center, University Children's Hospital, Zürich, CH-8032, Switzerland.
    Severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is caused by mutations in the MTHFR gene and results in hyperhomocysteinemia and varying severity of disease, ranging from neonatal lethal to adult onset. Including those described here, 109 MTHFR mutations have been reported in 171 families, consisting of 70 missense mutations, 17 that primarily affect splicing, 11 nonsense mutations, seven small deletions, two no-stop mutations, one small duplication, and one large duplication. Only 36% of mutations recur in unrelated families, indicating that most are "private. Read More

    Genet Couns 2015 ;26(4):425-30
    Cobalamin C (Cbl C) disease is an inborn error of intracellular cobalamin metabolism. Two distinct clinical types are defined according to the age of onset. We describe an 8 year old girl with late-onset Cbl C disease presenting with neuropsychiatric symptoms. Read More

    [Hereditary metabolic diseases with onset in adulthood. Early and correct treatment of acute symptoms can be life-saving].
    Lakartidningen 2016 Feb 1;113. Epub 2016 Feb 1.
    Karolinska universitetssjukhuset - Centrum för medfödda metabola sjukdomar Stockholm, Sweden arolinska universitetssjukhuset - Centrum för medfödda metabola sjukdomar Stockholm, Sweden.
    Inherited metabolic diseases usually present in the neonatal period or before school age. A growing portion of the disorders can be treated successfully, and an increasing number of patients are now treated in adult medicine. Several of the disorders also exist as attenuated variants without distinct symptoms in childhood. Read More

    A Whole-Cell Surface Plasmon Resonance Sensor Based on a Leucine Auxotroph of Escherichia coli Displaying a Gold-Binding Protein: Usefulness for Diagnosis of Maple Syrup Urine Disease.
    Anal Chem 2016 Mar 12;88(5):2871-6. Epub 2016 Feb 12.
    Department of Chemical and Biomolecular Engineering (BK21+ Program), KAIST , 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
    We developed a whole-cell surface plasmon resonance (SPR) sensor based on a leucine auxotroph of Escherichia coli displaying a gold-binding protein (GBP) in response to cell growth and applied this sensor to the diagnosis of maple syrup urine disease, which is represented by the elevated leucine level in blood. The leucine auxotroph was genetically engineered to grow displaying GBP in a proportion to the concentration of target amino acid leucine. The GBP expressed on the surface of the auxotrophs directly bound to the golden surface of an SPR chip without the need for any additional treatment or reagents, which consequently produced SPR signals used to determine leucine levels in a test sample. Read More

    Ophthalmic Manifestations and Long-Term Visual Outcomes in Patients with Cobalamin C Deficiency.
    Ophthalmology 2016 Mar 26;123(3):571-82. Epub 2016 Jan 26.
    National Human Genome Research Institute, Genetics and Molecular Biology Branch, National Institutes of Health, Bethesda, Maryland.
    Purpose: To explore the ocular manifestations of cobalamin C (cblC) deficiency, an inborn error of intracellular vitamin B12 metabolism.

    Design: Retrospective, observational case series.

    Participants: Twenty-five cblC patients underwent clinical and ophthalmic examination at the National Institutes of Health between August 2004 and September 2012. Read More

    Kinetic stability of cystathionine beta-synthase can be modulated by structural analogs of S-adenosylmethionine: Potential approach to pharmacological chaperone therapy for homocystinuria.
    Biochimie 2016 Jul 20;126:6-13. Epub 2016 Jan 20.
    Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address:
    Many pathogenic missense mutations in human cystathionine beta-synthase (CBS) cause misfolding of the mutant enzyme resulting in aggregation or rapid degradation of the protein. Subsequent loss of CBS function leads to CBS-deficient homocystinuria (CBSDH). CBS contains two sets of binding sites for S-adenosylmethionine (SAM) that independently regulate the enzyme activity and kinetically stabilize its regulatory domain. Read More

    Thioethers as markers of hydrogen sulfide production in homocystinurias.
    Biochimie 2016 Jul 11;126:14-20. Epub 2016 Jan 11.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
    Two enzymes in the transsulfuration pathway of homocysteine -cystathionine beta-synthase (CBS) and gamma-cystathionase (CTH)-use cysteine and/or homocysteine to produce the important signaling molecule hydrogen sulfide (H2S) and simultaneously the thioethers lanthionine, cystathionine or homolanthionine. In this study we explored whether impaired flux of substrates for H2S synthesis and/or deficient enzyme activities alter production of hydrogen sulfide in patients with homocystinurias. As an indirect measure of H2S synthesis we determined by LC-MS/MS concentrations of thioethers in plasma samples from 33 patients with different types of homocystinurias, in 8 patient derived fibroblast cell lines, and as reaction products of seven purified mutant CBS enzymes. Read More

    Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging.
    Compr Physiol 2015 Dec 15;6(1):471-505. Epub 2015 Dec 15.
    Pathology and Laboratory Medicine Service, West Roxbury, VA Boston Healthcare System, Harvard Medical School, Boston, Massachusetts, USA.
    The importance of homocysteine in vascular function and arteriosclerosis was discovered by demonstration of arteriosclerotic plaques in children with homocystinuria caused by inherited enzymatic deficiencies of cystathionine synthase, methionine synthase, or methylene-tetrahydrofolate reductase. According to the homocysteine theory of arteriosclerosis, an elevated blood homocysteine level is an important risk factor for atherosclerosis in subjects without these rare enzymatic abnormalities. The homocysteine theory is supported by demonstration of arterial plaques in experimental animals with hyperhomocysteinemia, by discovery of a pathway for conversion of homocysteine thiolactone to sulfate in cell cultures from children with homocystinuria, and by demonstration of growth promotion by homocysteic acid in normal and hypophysectomized animals. Read More

    Molecular and biochemical investigations of patients with intermediate or severe hyperhomocysteinemia.
    Mol Genet Metab 2016 Mar 23;117(3):344-50. Epub 2015 Dec 23.
    Centre for Haemophilia and Thrombosis, Department of Clinical Biochemistry Aarhus University Hospital, Denmark. Electronic address:
    A discrepancy has been identified between numbers of expected and identified patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency. Patients homozygous for the frequent c.833T>C (p. Read More

    Low bone mineral density is a common finding in patients with homocystinuria.
    Mol Genet Metab 2016 Mar 10;117(3):351-4. Epub 2015 Dec 10.
    The Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Pennsylvania, Philadelphia, PA 19104, United States; Perelman School of Medicine at the University of Pennsylvania, 34th and Civic Center Blvd, Pennsylvania, Philadelphia, PA 19104, United States.
    Homocystinuria (HCU) due to deficiency of cystathionine beta-synthetase is associated with increased plasma levels of homocysteine and methionine and is characterized by developmental delay, intellectual impairment, ocular defects, thromboembolism and skeletal abnormalities. HCU has been associated with increased risk for osteoporosis in some studies, but the natural history of HCU-related bone disease is poorly understood. The objective of this study was to characterize bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) in a multi-center, retrospective cohort of children and adults with HCU. Read More

    Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions.
    Eur J Dermatol 2016 Jan-Feb;26(1):64-7
    Juba University, Sudan.
    Background: Vitiligo is the most prevalent acquired pigmentary disorder as a result of destruction of melanocytes. Several studies have reported increased serum levels of homocysteine (Hcy) in vitiligo patients which may be the result of decreased Vitamin B12 and folic acid levels. In addition, homocystinuria is associated with pigmentary dilution. Read More

    Novel Compound Heterozygous CBS Mutations Cause Homocystinuria in a Han Chinese Family.
    Sci Rep 2015 Dec 15;5:17947. Epub 2015 Dec 15.
    Sichuan Provincial Key Laboratory for Disease Gene Study, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
    The cystathionine β-synthase (CBS) gene has been shown to be related to homocystinuria. This study was aimed to detect the mutations in CBS in a Han Chinese family with homocystinuria. A four-generation family from Shandong Province of China was recruited in this study. Read More

    Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.
    Invest Ophthalmol Vis Sci 2015 Dec;56(13):7875-87
    Scheie Eye Institute and the Perelman Center for Advanced Medicine, Department of Ophthamology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States 3Division of Ophthalmology, The Children's Hospital of.
    Purpose: To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease.

    Methods: Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Read More

    Sulfur amino acids and atherosclerosis: a role for excess dietary methionine.
    Ann N Y Acad Sci 2016 Jan 8;1363:18-25. Epub 2015 Dec 8.
    Nutrition and Brain Health Laboratory, The Institute of Biochemistry Food and Nutrition Science, The Robert H. Smith Faculty of Agriculture Food and the Environment, The Hebrew University of Jerusalem, Israel.
    The homocysteine theory of arteriosclerosis received credence when it was shown that after a methionine load, circulating homocysteine-cysteine concentrations were higher in cardiovascular disease patients than in healthy controls. Subsequent studies showing associations between homocysteine and coronary artery disease, stroke and cognitive impairment, relied on small increases in homocysteine concentration unlike the very high homocysteine seen in the rare genetic disorders that lead to homocystinuria and much higher homocysteine levels. Subsequent studies in cell culture, animals, and humans showed that a variety of cardiovascular adverse effects of "high homocysteine" introduced either as a nonphysiological bolus or as a methionine load led to high homocysteine. Read More

    Successive MRI Findings of Reversible Cerebral White Matter Lesions in a Patient with Cystathionine β-Synthase Deficiency.
    Tohoku J Exp Med 2015 ;237(4):323-7
    Department of Pediatrics, Graduate School of Medicine, Gifu University.
    Cystathionine β-synthase (CBS) deficiency, well known as classical homocystinuria, is a rare autosomal recessive inborn error of homocysteine and sulfur metabolism. CBS converts homocysteine to cystathionine. The clinical features of untreated CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Read More

    The effect of dietary modulation of sulfur amino acids on cystathionine β synthase-deficient mice.
    Ann N Y Acad Sci 2016 Jan 24;1363:80-90. Epub 2015 Nov 24.
    Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
    Cystathionine β synthase (CBS) is a key enzyme in the methionine and cysteine metabolic pathway, acting as a metabolic gatekeeper to regulate the flow of fixed sulfur from methionine to cysteine. Mutations in the CBS gene cause clinical CBS deficiency, a disease characterized by elevated plasma total homocysteine (tHcy) and methionine and decreased plasma cysteine. The treatment goal for CBS-deficient patients is to normalize the metabolic values of these three metabolites using a combination of vitamin therapy and dietary manipulation. Read More

    Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China.
    Brain Dev 2016 May 10;38(5):491-7. Epub 2015 Nov 10.
    Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, Shandong Province, China; Jinan Maternal and Child Care Hospital, Jinan 250001, Shandong Province, China; Department of Immunology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. Electronic address:
    Objectives: To estimate the incidence of MMA on newborn screening in Shandong province from May 2011 to May 2014 and summarize the clinical presentation, biochemical features, mutation analysis, and treatment regime of early-treated patients with cblC disease.

    Methods: Between May 2011 and May 2014, 35,291 newborns were screened for MMA in Jinan maternal and Child Care Hospital, Shandong province. The levels of C3, C3/C2, methionine and tHcy were measured. Read More

    Genetic analysis of four cases of methylmalonic aciduria and homocystinuria, cblC type#.
    Int J Clin Exp Pathol 2015 1;8(8):9337-41. Epub 2015 Aug 1.
    Department of Neurology, Capital Institute of Pediatrics Beijing, PR China.
    Methylmalonic aciduria and homocystinuria, cblC type, is the most common disorder of intracellular vitamin B12 (cobalamin, cbl) metabolism, which results in impaired biosynthesis of methylcobalamin and adenosylcobalamin. The gene MMACHC responsible for the cblC type had been identified, which enables molecular diagnostics. Here, we report four cblC type cases, which were identified by the typical manifestations, and a new approach of next-generation sequencing platform in pediatrics for genetic diseases, further confirmed by Sanger sequencing of the whole MMACHC gene. Read More

    Newborn screening for homocystinuria.
    Cochrane Database Syst Rev 2015 Oct 1(10):CD008840. Epub 2015 Oct 1.
    Willink Biochemical Genetics Unit, Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, St Mary's Hospital, Oxford Road, Manchester, UK, M13 9WL.
    Background: Homocystinuria is a rare inherited disorder due to a deficiency in cystathionine beta synthase. Individuals with this condition appear normal at birth but develop serious complications in childhood. Diagnosis and treatment started sufficiently early in life can effectively prevent or reduce the severity of these complications. Read More

    Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias.
    Clin Chim Acta 2015 Oct 11;450:342-8. Epub 2015 Sep 11.
    Newborn Screening, Biochemistry and Pharmacology Laboratory, Pediatric Neurology Unit and Laboratories, Meyer Children's University Hospital, Florence, Italy. Electronic address:
    Background: 3-Hydroxypalmitoleoyl-carnitine (C16:1-OH) has recently been reported to be elevated in acylcarnitine profiles of patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency.

    Methods: The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. Read More

    Structure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases.
    J Biol Chem 2015 Dec 13;290(49):29155-66. Epub 2015 Sep 13.
    From the Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 and
    In mammals, B12 (or cobalamin) is an essential cofactor required by methionine synthase and methylmalonyl-CoA mutase. A complex intracellular pathway supports the assimilation of cobalamin into its active cofactor forms and delivery to its target enzymes. MMADHC (the methylmalonic aciduria and homocystinuria type D protein), commonly referred to as CblD, is a key chaperone involved in intracellular cobalamin trafficking, and mutations in CblD cause methylmalonic aciduria and/or homocystinuria. Read More

    Clinical presentation, etiology, and outcome of stroke in children: A hospital-based study.
    Brain Dev 2016 Feb 2;38(2):204-8. Epub 2015 Sep 2.
    Department of Pediatrics, Division of Pediatric Cardiology, Faculty of Medicine, The University of Jordan, Jordan.
    Aim: To describe clinical presentations, etiologies, and outcomes of stroke in Jordanian children.

    Patients And Methods: We retrospectively reviewed the medical records of children diagnosed with ischemic stroke who presented to our clinic from January 2001 to June 2014. Patients with onset of stroke in the neonatal period were excluded. Read More

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