2,249 results match your criteria Homocystinuria


Long-term uninterrupted enzyme replacement therapy prevents liver disease in murine model of severe homocystinuria.

Hum Mutat 2020 Jul 5. Epub 2020 Jul 5.

Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Classical homocystinuria (HCU) is an inborn error of metabolism caused by loss of cystathionine beta-synthase (CBS) activity with concomitant buildup of homocysteine. In KO mice, a mouse model of HCU, complete lack of CBS is neonatally lethal. Administration of OT-58, an enzyme therapy for HCU, during the first five weeks of life rescued KO mice survival by preventing liver disease. Read More

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http://dx.doi.org/10.1002/humu.24072DOI Listing

Bilateral Ectopia Lentis in Classical Homocystinuria.

QJM 2020 Jun 29. Epub 2020 Jun 29.

Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh-160012, India.

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http://dx.doi.org/10.1093/qjmed/hcaa191DOI Listing

Laboratory evaluation of homocysteine remethylation disorders and classic homocystinuria: Long-term follow-up using a cohort of 123 patients.

Clin Chim Acta 2020 Jun 10;509:126-134. Epub 2020 Jun 10.

Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, United States; ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, United States.

The homocystinurias, caused by defects of remethylation and cystathionine-beta-synthase (CBS) deficiency, are characterized by elevated homocysteine and abnormal methionine levels. Various treatments, including injectable hydroxycobalamin and oral betaine, aim to reduce homocysteine toxicity and normalize methionine, but only limited biochemical data has been reported assessing biochemical response to treatment. We analyzed laboratory results in 812 plasma samples from 56 patients with remethylation disorders and 67 patients with CBS deficiency. Read More

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http://dx.doi.org/10.1016/j.cca.2020.06.014DOI Listing

The human B12 trafficking protein CblC processes nitrocobalamin.

J Biol Chem 2020 May 26. Epub 2020 May 26.

University of Michigan, United States.

In humans, cobalamin or vitamin B12 is delivered to two target enzymes via a complex intracellular trafficking pathway comprising transporters and chaperones. CblC (or MMACHC) is a processing chaperone that catalyzes an early step in this trafficking pathway. CblC removes the upper axial ligand of cobalamin derivatives, forming an intermediate in the pathway that is subsequently converted to the active cofactor derivatives. Read More

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http://dx.doi.org/10.1074/jbc.RA120.014094DOI Listing

CRY1-CBS binding regulates circadian clock function and metabolism.

FEBS J 2020 May 8. Epub 2020 May 8.

Department of Molecular Biology and Genetics, Koc University, Istanbul, Turkey.

Circadian disruption influences metabolic health. Metabolism modulates circadian function. However, the mechanisms coupling circadian rhythms and metabolism remain poorly understood. Read More

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http://dx.doi.org/10.1111/febs.15360DOI Listing
May 2020
4.001 Impact Factor

Sequential multiple retinal vein occlusions and transient ischemic attack in MTHFR polymorphism and protein S deficiency.

Mol Genet Genomic Med 2020 Jul 28;8(7):e1273. Epub 2020 Apr 28.

Department of Ophthalmology, Columbia University, New York, NY, USA.

Background: The C677T variant of the MTHFR (5,10-Methylenetetrahydrofolate reductase) gene is associated with increased susceptibility to homocystinuria (OMIM#236250), neural tube defects (OMIM#601634), schizophrenia (OMIM#181500), thromboembolism (OMIM#188050), and vascular diseases. Protein S deficiency is also associated with an increased risk of thromboembolism from reduced thrombin generation. In this report, we describe the case of a patient who presented with multiple retinal vein occlusions likely caused by an underlying combination of a homozygous MTHFR C677T variant and protein S deficiency. Read More

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http://dx.doi.org/10.1002/mgg3.1273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336745PMC

Inborn errors of metabolism detectable by tandem mass spectrometry in Beijing.

J Pediatr Endocrinol Metab 2020 May;33(5):639-645

Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang District, Beijing, P.R. China.

Background Individual inborn errors of metabolism (IEMs) are rare disorders. Expanded newborn screening for IEMs by tandem mass spectrometry (TMS) is an efficient approach for early diagnosis. Here we provide the newborn screening program for the application of this approach (between July 2014 and March 2019) to the identification of newborns in Beijing at risk of developing a potentially fatal disease. Read More

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http://dx.doi.org/10.1515/jpem-2019-0420DOI Listing

Pharmacologic pupillary constriction after dilated fundus examination for ectopia lentis to prevent further subluxation.

Am J Ophthalmol Case Rep 2020 Jun 7;18:100694. Epub 2020 Apr 7.

Division of Cornea, Cataracts and External Diseases, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Purpose: To describe two cases of ectopia lentis with different preoperative management strategies following the initial diagnostic dilated exam.

Observations: In both cases, the patients presented with bilateral subluxation of the crystalline lens. Neither patient had a known history of Marfan's disease, homocystinuria or other systemic disorders that affect the body's connective tissue possibly leading to lens subluxation. Read More

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http://dx.doi.org/10.1016/j.ajoc.2020.100694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153168PMC

Analysis of Total Thiols in the Urine of a Cystathionine β-Synthase-Deficient Mouse Model of Homocystinuria Using Hydrophilic Interaction Chromatography.

Molecules 2020 Apr 9;25(7). Epub 2020 Apr 9.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 1130033, Japan.

Homocysteine and related thiols (cysteine, cysteinylglycine, and glutathione) in the urine of a cystathionine β-synthase (CBS)-deficient mouse model were quantified using hydrophilic interaction chromatography with fluorescence detection. Urine samples were incubated with tris(2-carboxyethyl) phosphine to reduce disulfide bonds into thiols. After deproteinization, thiols were fluorescently derivatized with ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F). Read More

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http://dx.doi.org/10.3390/molecules25071735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181027PMC

Brain Circuit Alterations and Cognitive Disability in Late-Onset Cobalamin D Disorder.

J Clin Med 2020 Apr 2;9(4). Epub 2020 Apr 2.

Computational Neuroimaging Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.

Neuroimaging studies describing brain circuits' alterations in cobalamin (vitamin B12)-deficient patients are limited and have not been carried out in patients with inborn errors of cobalamin metabolism. The objective of this study was to assess brain functionality and brain circuit alterations in a patient with an ultra-rare inborn error of cobalamin metabolism, methylmalonic aciduria, and homocystinuria due to cobalamin D disease, as compared with his twin sister as a healthy control (HC). We acquired magnetic resonance imaging (including structural, functional, and diffusion images) to calculate brain circuit abnormalities and combined these results with the scores after a comprehensive neuropsychological evaluation. Read More

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http://dx.doi.org/10.3390/jcm9040990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231091PMC

The Spectrum of Mutations of Homocystinuria in the MENA Region.

Genes (Basel) 2020 03 20;11(3). Epub 2020 Mar 20.

Biomedical Research Center, Qatar University, P.O. Box 2713 Doha, Qatar.

Homocystinuria is an inborn error of metabolism due to the deficiency in cystathionine beta-synthase (CBS) enzyme activity. It leads to the elevation of both homocysteine and methionine levels in the blood and urine. Consequently, this build-up could lead to several complications such as nearsightedness, dislocated eye lenses, a variety of psychiatric and behavioral disorders, as well as vascular system complications. Read More

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http://dx.doi.org/10.3390/genes11030330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140887PMC

Classical homocystinuria: A common inborn error of metabolism? An epidemiological study based on genetic databases.

Mol Genet Genomic Med 2020 Jun 30;8(6):e1214. Epub 2020 Mar 30.

Department of Clinical Genetics, Center for Lysosomal and Metabolic Diseases, ErasmusMC, Rotterdam, The Netherlands.

Background: Biallelic pathogenic variants in CBS gene cause the most common form of homocystinuria, the classical homocystinuria (HCU). The worldwide prevalence of HCU is estimated to be 0.82:100,000 [95% CI, 0. Read More

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http://dx.doi.org/10.1002/mgg3.1214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284035PMC

Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult.

BMC Nephrol 2020 Mar 12;21(1):96. Epub 2020 Mar 12.

Nephrology, Dialysis and Transplantation Department, CHU Clermont Ferrand, University Clermont Auvergne, Clermont Ferrand, France.

Background: Thrombotic microangiopathy (TMA) syndromes are characterized by the association of hemolytic anemia, thrombocytopenia and organ injury due to arteriolar and capillary thrombosis.

Case Presentation: We report the first case of adult onset cobalamin C (Cbl C) disease associated with anti-factor H antibody-associated hemolytic uremic syndrome (HUS). A 19-year-old woman was admitted to the nephrology department owing to acute kidney failure, proteinuria, and hemolytic anemia with schizocytes. Read More

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http://dx.doi.org/10.1186/s12882-020-01748-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066776PMC

Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease.

J Inherit Metab Dis 2020 Mar 11. Epub 2020 Mar 11.

Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado, Aurora, Colorado.

Hydrogen sulfide, a signaling molecule formed mainly from cysteine, is catabolized by sulfide:quinone oxidoreductase (gene SQOR). Toxic hydrogen sulfide exposure inhibits complex IV. We describe children of two families with pathogenic variants in SQOR. Read More

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http://dx.doi.org/10.1002/jimd.12232DOI Listing

Cystathionine beta synthase deficiency and brain edema associated with methionine excess under betaine supplementation: Four new cases and a review of the evidence.

JIMD Rep 2020 Mar 8;52(1):3-10. Epub 2020 Jan 8.

Department of Pediatrics, Division of Biochemical Genetics, Rady Children's Hospital-San Diego University of California San Diego California.

CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. Read More

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http://dx.doi.org/10.1002/jmd2.12092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052692PMC

Prevalence, characteristics, and costs of diagnosed homocystinuria, elevated homocysteine, and phenylketonuria in the United States: a retrospective claims-based comparison.

BMC Health Serv Res 2020 Mar 6;20(1):183. Epub 2020 Mar 6.

IBM Watson Health, 75 Binney St, Cambridge, MA, 02142, USA.

Background: Classical homocystinuria (HCU), an inborn error of homocysteine metabolism, has previously been estimated to affect approximately 1 in 100,000-200,000 people in the United States (US). HCU is poorly detected by newborn screening, resulting in underestimates of its prevalence. This study compared characteristics, healthcare use and costs, and projected prevalence between patients with diagnosed HCU, elevated total homocysteine (tHcy), and diagnosed phenylketonuria (PKU). Read More

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http://dx.doi.org/10.1186/s12913-020-5054-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059682PMC

Is the gut microbiota dysbiotic in patients with classical homocystinuria?

Biochimie 2020 Jun 24;173:3-11. Epub 2020 Feb 24.

PostGraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Laboratory of Basic Research and Advanced Investigations in Neuroscience (BRAIN), Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduation Program in Medicine: Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address:

Classical homocystinuria (HCU) is characterized by increased plasma levels of total homocysteine (tHcy) and methionine (Met). Treatment may involve supplementation of B vitamins and essential amino acids, as well as restricted Met intake. Dysbiosis has been described in some inborn errors of metabolism, but has not been investigated in HCU. Read More

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http://dx.doi.org/10.1016/j.biochi.2020.02.013DOI Listing

Multiple sclerosis and intracellular cobalamin defect (/) comorbidity in a young male.

Mol Genet Metab Rep 2020 Mar 7;22:100560. Epub 2020 Jan 7.

Sapienza University of Rome, Department of Human Neuroscience, Rome, Italy.

Background: Methylmalonic acidaemia with homocystinuria type C (cblC defect) is an inherited error of cobalamin metabolism. Cobalamin deficient processing results in high levels of methylmalonic acid and homocysteine. The latter is considered to be a risk factor for multiple sclerosis (MS). Read More

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http://dx.doi.org/10.1016/j.ymgmr.2019.100560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026611PMC

High-dose hydroxocobalamin achieves biochemical correction and improvement of neuropsychiatric deficits in adults with late onset cobalamin C deficiency.

JIMD Rep 2020 Jan 13;51(1):17-24. Epub 2019 Dec 13.

Department of Genetic Medicine and Pediatrics Johns Hopkins University Baltimore Maryland.

Cobalamin C () deficiency is the most common inborn error of intracellular cobalamin metabolism caused by pathogenic variant(s) in and manifests with methylmalonic acidemia, hyperhomocysteinemia, and hypomethioninemia with a variable age of presentation. Individuals with late-onset may be asymptomatic until manifesting neuropsychiatric symptoms, thromboembolic events, and renal disease. Although hydroxocobalamin provides a foundation for therapy, optimal dose regimen for adult patients has not been systematically evaluated. Read More

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http://dx.doi.org/10.1002/jmd2.12087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012733PMC
January 2020

Generation of a Human iPSC line (SDQLCHi021-A) from a patient with methylmalonic acidemia cblC type carrying compound heterozygous mutations in MMAHC gene.

Stem Cell Res 2020 03 16;43:101709. Epub 2020 Jan 16.

Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Jinan, Shandong, 250022, China. Electronic address:

Methylmalonic acidemia and homocystinuria, cblC type is a rare autosomal recessive inheritance disease. Its clinical phenotype involves multiple systems with varying degrees of severity. The disease is caused by the mutations in the MMACHC gene located on chromosome 1p34. Read More

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http://dx.doi.org/10.1016/j.scr.2020.101709DOI Listing

Estimated prevalence of moderate to severely elevated total homocysteine levels in the United States: A missed opportunity for diagnosis of homocystinuria?

Mol Genet Metab 2020 05 5;130(1):36-40. Epub 2020 Feb 5.

IBM Watson Health, 75 Binney St, Cambridge, MA 02142, USA. Electronic address:

Classical homocystinuria (HCU) is a genetic disorder caused by mutations in the cystathionine beta synthase gene, which results in impaired metabolism of the sulfur-bearing amino acid homocysteine and its accumulation in blood and tissues. Classical HCU can be detected via newborn screening in the United States, but the test is widely acknowledged to miss many patients. While severely elevated homocysteine levels (>100 μmol /L) frequently lead to a classical HCU diagnosis, intermediate levels (>30 to 100 μmol /L), though linked to many of the known complications of HCU, are not always recognized as associated with HCU. Read More

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http://dx.doi.org/10.1016/j.ymgme.2020.02.001DOI Listing

Intraoperative optical coherence tomography-guided release of lenticulo-corneal adhesion and lens aspiration in anterior dislocation of lens with corneal edema.

Indian J Ophthalmol 2020 03;68(3):510-512

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

Purpose: To describe the outcome of microscope integrated optical coherence tomography (MiOCT) guided removal of lenticulo-corneal adhesion and intralenticular lens aspiration (ILLA) in cases with anterior dislocation of the crystalline lens and corneal edema.

Methods: MiOCT-guided ILLA was performed in three eyes of two cases of homocystinuria with spontaneous anterior dislocation of lens and corneal edema. Lenticulo-corneal adhesion was noted intraoperatively, which was not apparent pre-operatively. Read More

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http://dx.doi.org/10.4103/ijo.IJO_1329_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043159PMC
March 2020
0.927 Impact Factor

Ventricular assist device bridge to heart transplantation in a child with homocystinuria.

J Heart Lung Transplant 2020 Mar 28;39(3):282-283. Epub 2019 Dec 28.

Department of Surgery & Pediatrics, UF Shand's Congenital Heart Center, Gainsville Florida.

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http://dx.doi.org/10.1016/j.healun.2019.12.003DOI Listing
March 2020
6.650 Impact Factor

A proactive genotype-to-patient-phenotype map for cystathionine beta-synthase.

Genome Med 2020 01 30;12(1):13. Epub 2020 Jan 30.

The Donnelly Centre, University of Toronto, Toronto, ON, M5S 3E1, Canada.

Background: For the majority of rare clinical missense variants, pathogenicity status cannot currently be classified. Classical homocystinuria, characterized by elevated homocysteine in plasma and urine, is caused by variants in the cystathionine beta-synthase (CBS) gene, most of which are rare. With early detection, existing therapies are highly effective. Read More

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http://dx.doi.org/10.1186/s13073-020-0711-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993387PMC
January 2020

Mutational landscape screening of methylene tetrahydrofolate reductase to predict homocystinuria associated variants: An integrative computational approach.

Mutat Res 2020 Jan - Apr;819-820:111687. Epub 2020 Jan 16.

Centre for Bioinformatics, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Sankara Nethralaya, Chennai, 600 006, Tamil Nadu, India. Electronic address:

Methylene tetrahydrofolate reductase (MTHFR) is a flavoprotein, involved in one-carbon pathway and is responsible for folate and homocysteine metabolism. Regulation of MTHFR is pivotal for maintaining the cellular concentrations of methionine and SAM (S-adenosyl methionine) which are essential for the synthesis of nucleotides and amino acids, respectively. Therefore, mutations in MTHFR leads to its dysfunction resulting in conditions like homocystinuria, cardiovascular diseases, and neural tube defects in infants. Read More

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http://dx.doi.org/10.1016/j.mrfmmm.2020.111687DOI Listing

Novel method for l-methionine determination using l-methionine decarboxylase and application of the enzyme for l-homocysteine determination.

Biosci Biotechnol Biochem 2020 May 20;84(5):927-935. Epub 2020 Jan 20.

Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan.

For many years, clinical studies have suggested that blood levels of l-methionine and L-homocysteine correlate with health status or homocystinuria/hypermethioninemia. l-Methionine in a solution containing 0%, 10%, or 20% human serum was detected in 10-200 µM using l-methionine decarboxylase (MetDC). Spike and recovery tests showed that the enzymatic assay could accurately and reproducibly determine the increases in l-methionine in serum samples. Read More

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http://dx.doi.org/10.1080/09168451.2020.1715781DOI Listing

The correlation between the evolution of bilateral basal ganglia hemorrhage using MR imaging and neurological damage recovery in an infant with methylmalonic aciduria.

Brain Dev 2020 Apr 11;42(4):357-362. Epub 2020 Jan 11.

Shandong Medical Imaging Research Institute Affiliated to Shandong University, Jing-wu Road No. 324, Jinan 250021, Shandong, China. Electronic address:

Purpose: We report on one patient with methylmalonic acidemia (MMA) who presented with symmetrical hemorrhage of the caudate nucleus accompanied by severe ventricular dilatation, follow-up magnetic resonance imaging (MRI) findings from one year later, and the clinical manifestations, neuropsychological scores, genetic test results, urine and blood laboratory results and evolution of the disorder.

Materials And Methods: This study describes the recent and remote neuropathologic findings, reviews the literature, and discusses the possible pathogenetic mechanisms of these central nervous system lesions.

Results: Patients with MMA may have signs of basal ganglia hemorrhage during acute onset, and the hemorrhage may disappear after treatment. Read More

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http://dx.doi.org/10.1016/j.braindev.2019.12.011DOI Listing

Classical homocystinuria: From cystathionine beta-synthase deficiency to novel enzyme therapies.

Biochimie 2020 Jun 16;173:48-56. Epub 2019 Dec 16.

Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. Electronic address:

Genetic defects in cystathionine beta-synthase (CBS), a key enzyme of organic sulfur metabolism, result in deficiency of CBS activity and a rare inborn error of metabolism called classical homocystinuria (HCU). HCU is characterized by massive accumulation of homocysteine, an intermediate of methionine metabolism, and multisystemic clinical symptoms. Current treatment options for HCU are very limited and often inefficient, partially due to a low patient compliance with very strict dietary regimen. Read More

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http://dx.doi.org/10.1016/j.biochi.2019.12.007DOI Listing

Methylmalonic Acidemia Complicated by Homocystinuria Diseases: a Report of Three Cases.

Adv Ther 2020 01 22;37(1):630-636. Epub 2019 Nov 22.

Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China.

This study aims to improve our understanding of methylmalonic acidemia (MMA) complicated by homocystinuria disease by analyzing the clinical characteristics, treatment response and prognosis of three patients. Hyperhomocysteinemia and developmental retardation were present in all patients, epilepsy was present in one patient, and hemolytic uremic syndrome was present in one patient. The conditions of two patients were complicated by pulmonary arterial hypertension, one patient by left pulmonary vein ectopic drainage to the coronary sinus and the other by noncompaction of the ventricular myocardium. Read More

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http://dx.doi.org/10.1007/s12325-019-01149-4DOI Listing
January 2020

Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419858572

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. Read More

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http://dx.doi.org/10.1177/2058738419858572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822179PMC

Hypermethioninemia in Campania: Results from 10 years of newborn screening.

Mol Genet Metab Rep 2019 Dec 11;21:100520. Epub 2019 Oct 11.

Department of Molecular Medicine and Medical Biotechnologies, "Federico II" University, Naples, Italy.

In the last years tandem mass spectrometry (MS/MS) has become a leading technology used for neonatal screening purposes. Newborn screening by MS/MS on dried blood spot samples (DBS) has one of its items in methionine levels: the knowledge of this parameter allows the identification of infant affected by homocystinuria (cystathionine β-synthase, CBS, deficiency) but can also lead, as side effect, to identify cases of methionine adenosyltransferase (MAT) type I/III deficiency. We started an expanded newborn screening for inborn errors of metabolism in Campania region in 2007. Read More

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http://dx.doi.org/10.1016/j.ymgmr.2019.100520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796781PMC
December 2019

Isolated subacute combined degeneration in late-onset cobalamin C deficiency in children: Two case reports and literature review.

Medicine (Baltimore) 2019 Sep;98(39):e17334

Second Department of Neurology, The Children's Hospital of Hebei Province.

Rationale: Subacute combined degeneration (SCD) is a disease caused by decreased vitamin B12 intake or metabolic disorders. It is more common in the elderly and rarely seen in children. Here, we report 2 pediatric cases of SCD in late-onset cobalamin C (CblC) deficiency. Read More

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http://dx.doi.org/10.1097/MD.0000000000017334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775410PMC
September 2019
2 Reads

Parenteral hydroxocobalamin dose intensification in five patients with different types of early onset intracellular cobalamin defects: Clinical and biochemical responses.

JIMD Rep 2019 Sep 1;49(1):70-79. Epub 2019 Jul 1.

Pediatric Neurology and Metabolism UZ-VUB, Vrije Universiteit Brussels Brussels Belgium.

Intracellular cobalamin metabolism (ICM) defects can be present as autosomal recessive or X-linked disorders. Parenteral hydroxocobalamin (P-OHCbl) is the mainstay of therapy, but the optimal dose has not been determined. Despite early treatment, long-term complications may develop. Read More

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http://dx.doi.org/10.1002/jmd2.12055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718108PMC
September 2019
3 Reads

Prospective evaluation of pregnancy outcome in an Italian woman with late-onset combined homocystinuria and methylmalonic aciduria.

BMC Pregnancy Childbirth 2019 Aug 30;19(1):318. Epub 2019 Aug 30.

Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Foggia, Italy.

Background: Cobalamin metabolism disorders are rare, inherited diseases which cause megaloblastic anaemia and other clinical manifestations. Early diagnosis of these conditions is essential, in order to allow appropriate treatment as early as possible.

Case Presentation: Here we report the case of a patient who was apparently healthy until the age of 20, when she presented with impaired renal function and normocytic anaemia. Read More

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http://dx.doi.org/10.1186/s12884-019-2474-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716909PMC
August 2019
3 Reads

Behavior, body composition, and vascular phenotype of homocystinuric mice on methionine-restricted diet or enzyme replacement therapy.

FASEB J 2019 11 26;33(11):12477-12486. Epub 2019 Aug 26.

Section of Genetics, Department of Pediatrics, School of Medicine, University of Colorado, Aurora, Colorado, USA.

Classic homocystinuria (HCU) is an inherited disorder characterized by elevated homocysteine (Hcy) in plasma and tissues resulting from cystathionine β-synthase (CBS) deficiency. There is no cure, and patients are predominantly managed by methionine-restricted diet (MRD) to limit the production of Hcy. In this study, we used the I278T mouse model of HCU to evaluate the long-term impact of a novel enzyme replacement therapy [truncated human CBS C15S mutant modified with linear 20-kDa -hydroxysuccinimide ester polyethylene glycol (OT-58)] on clinical end points relevant to human patients with HCU. Read More

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http://dx.doi.org/10.1096/fj.201901203RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902697PMC
November 2019
11 Reads

Folate, genomic stability and colon cancer: The use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring.

Mutat Res 2019 07 5;843:73-80. Epub 2018 Sep 5.

Natural Products Group, Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK; School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, UK. Electronic address:

Intake of folate (vitamin B) is strongly inversely linked with human cancer risk, particularly colon cancer. In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing colon cancer. Read More

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http://dx.doi.org/10.1016/j.mrgentox.2018.08.012DOI Listing
July 2019
9 Reads

Hyperhomocysteinemia: a trigger for complement-mediated TMA?

Acta Clin Belg 2019 Aug 11:1-5. Epub 2019 Aug 11.

a Department of Nephrology, University Hospitals Leuven , Leuven , Belgium.

A 34-year-old man of North African descent was referred to the emergency department because of malignant hypertension (220/113 mmHg), acute visual disturbances and acute kidney failure (serum creatinine 14.0 mg/dL). Blood analysis was compatible with thrombotic microangiopathy (TMA). Read More

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http://dx.doi.org/10.1080/17843286.2019.1649039DOI Listing
August 2019
3 Reads

Biochemical Screening of Intellectually Disabled Patients: A Stepping Stone to Initiate a Newborn Screening Program in Pakistan.

Front Neurol 2019 17;10:762. Epub 2019 Jul 17.

Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan.

Inborn errors of metabolism (IEMs) are rare group of genetic disorders comprising of more than 1,000 different types. Around 200 of IEMs are potentially treatable through diet, pharmacological and other therapies, if diagnosed earlier in life. IEMs can be diagnosed early through newborn screening (NBS) programs, which are in place in most of the developed countries. Read More

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http://dx.doi.org/10.3389/fneur.2019.00762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650569PMC
July 2019
5 Reads

Beyond evidence-based treatment of bipolar disorder: Rational pragmatic approaches to management.

Bipolar Disord 2019 11 19;21(7):650-659. Epub 2019 Aug 19.

Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

The evidence for efficacy of many currently available treatments for bipolar disorder is based on studies of nonrefractory patients with bipolar disorder. Therefore, not surprisingly, most treatment recommendations and guidelines for the treatment of bipolar disorder and its many comorbidities depend heavily on data from placebo controlled randomized clinical trials (RCTs), but these RCTs provide little direction for the clinician as to what next steps might be optimal in non- or partial-responders and in those with ongoing medical and psychiatric comorbidities. Given this and the paucity of RCTs at later treatment junctures, we thought it appropriate to begin a discussion of the quality of the data that some experts in the field might consider using in choosing and sequencing drugs and their combination. Read More

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http://dx.doi.org/10.1111/bdi.12813DOI Listing
November 2019
11 Reads

Assessing computational predictions of the phenotypic effect of cystathionine-beta-synthase variants.

Hum Mutat 2019 09 3;40(9):1530-1545. Epub 2019 Sep 3.

Department of Microbiology, Miami University, Oxford, Ohio.

Accurate prediction of the impact of genomic variation on phenotype is a major goal of computational biology and an important contributor to personalized medicine. Computational predictions can lead to a better understanding of the mechanisms underlying genetic diseases, including cancer, but their adoption requires thorough and unbiased assessment. Cystathionine-beta-synthase (CBS) is an enzyme that catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine, and in which variations are associated with human hyperhomocysteinemia and homocystinuria. Read More

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http://dx.doi.org/10.1002/humu.23868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325732PMC
September 2019
7 Reads
5.144 Impact Factor

Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review.

Eur J Med Genet 2019 Oct 4;62(10):103713. Epub 2019 Jul 4.

Tianjin Pediatric Research Institute, Tianjin Children's Hospital, Tianjin, 300134, China. Electronic address:

Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.103713DOI Listing
October 2019
1 Read

Traboulsi syndrome due to ASPH mutation: an under-recognised cause of ectopia lentis.

Clin Dysmorphol 2019 Oct;28(4):184-189

Department of Paediatric Ophthalmology, Manchester Royal Eye Hospital.

Traboulsi syndrome is an extremely rare ophthalmological disorder characterised by facial dysmorphism, lens dislocation, anterior segment abnormalities and spontaneous filtering blebs. It is caused by pathogenic variants in the ASPH gene. To date, only 13 individuals with Traboulsi syndrome from three families have been reported in the literature. Read More

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http://dx.doi.org/10.1097/MCD.0000000000000287DOI Listing
October 2019
4 Reads

Epidemiology of rare diseases detected by newborn screening in the Czech Republic.

Cent Eur J Public Health 2019 Jun;27(2):153-159

Department of Children and Adolescents, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic.

Objectives: Presymptomatic detection of patients with rare diseases (RD), defined by a population frequency less than 1 : 2,000, is the task of newborn screening (NBS). In the Czech Republic (CZ), currently eighteen RD are screened: phenylketonuria/hyperphenylalaninemia (PKU/HPA), congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), cystic fibrosis (CF), medium chain acyl-CoA dehydrogenase deficiency (MCADD), long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), very long chain acyl-CoA dehydrogenase deficiency (VLCADD), carnitine palmitoyl transferase I and II deficiency (CPTID, CPTIID), carnitine-acylcarnitine translocase deficiency (CACTD), maple syrup urine disease (MSUD), glutaric aciduria type I (GA I), isovaleryl-CoA dehydrogenase deficiency (IVA), argininemia (ARG), citrullinemia (CIT), biotinidase deficiency (BTD), cystathionine beta-synthase-deficient homocystinuria (CBSD HCU), and methylenetetrahydrofolate reductase deficiency homocystinuria (MTHFRD HCU). The aim was to analyze the prevalence of RD screened by NBS in CZ. Read More

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http://dx.doi.org/10.21101/cejph.a5441DOI Listing
June 2019
8 Reads

Analysis of the Qatari R336C cystathionine β-synthase protein in mice.

J Inherit Metab Dis 2019 09 10;42(5):831-838. Epub 2019 Jul 10.

Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Classical homocystinuria is a recessive inborn error of metabolism caused by mutations in the cystathionine beta-synthase (CBS) gene. The highest incidence of CBS deficiency in the world is found in the country of Qatar due to the combination of high rates of consanguinity and the presence of a founder mutation, c.1006C>T (p. Read More

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http://dx.doi.org/10.1002/jimd.12140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336392PMC
September 2019
12 Reads

Plasma methionine concentrations and incidence of hypermethioninemic encephalopathy during infancy in a large cohort of 36 patients with classical homocystinuria in the Republic of Ireland.

JIMD Rep 2019 May 26;47(1):41-46. Epub 2019 Mar 26.

National Centre for Inherited Metabolic Disorders Temple Street Children's University Hospital Dublin Ireland.

Background: Classical homocystinuria is an autosomal recessive disorder caused by profound cystathionine β-synthase deficiency. Its biochemical hallmarks are high concentrations of plasma homocyst(e)ine and methionine. Clinical manifestations include lens dislocation, developmental delay, skeletal anomalies, or thromboembolism. Read More

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http://dx.doi.org/10.1002/jmd2.12029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498867PMC
May 2019
5 Reads

Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents.

Pathobiology 2019 25;86(4):190-200. Epub 2019 Jun 25.

Laboratoire de génétique, immunologie et pathologie humaine, faculté des sciences de Tunis, Université El Manar II, Tunis, Tunisia.

Objective: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population.

Methods: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. Read More

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http://dx.doi.org/10.1159/000499498DOI Listing
December 2019
9 Reads
2.319 Impact Factor

The effectiveness of correcting abnormal metabolic profiles.

J Inherit Metab Dis 2020 Jan 17;43(1):2-13. Epub 2019 Jul 17.

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

Inborn errors of metabolism cause disease because of accumulation of a metabolite before the blocked step or deficiency of an essential metabolite downstream of the block. Treatments can be directed at reducing the levels of a toxic metabolite or correcting a metabolite deficiency. Many disorders have been treated successfully first in a single patient because we can measure the metabolites and adjust treatment to get them as close as possible to the normal range. Read More

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http://dx.doi.org/10.1002/jimd.12139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041635PMC
January 2020
26 Reads

Abnormal Amino Acid Profiles of Blood and Cerebrospinal Fluid from Cystathionine β-Synthase-Deficient Mice, an Animal Model of Homocystinuria.

Biol Pharm Bull 2019 ;42(6):1054-1057

Department of Health Chemistry, Showa Pharmaceutical University.

Mental retardation is the most common feature among inborn errors of amino acid metabolism. Patients with homocystinuria/homocysteinemia caused by cystathionine β-synthase (CBS) deficiency suffer from thromboembolism and mental retardation from early ages; therefore, detection by newborn screening is performed. Furthermore, elevated levels of serum homocysteine during pregnancy are associated with the occurrence of neural tube defects (NTDs) in newborns. Read More

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http://dx.doi.org/10.1248/bpb.b19-00127DOI Listing
November 2019
10 Reads