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    2080 results match your criteria Homocystinuria

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    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

    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

    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

    [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 2017 May 11;32(5):733-741. 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

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