2,406 results match your criteria Homocystinuria

Toxic Metabolites and Inborn Errors of Amino Acid Metabolism: What One Informs about the Other.

Metabolites 2022 Jun 8;12(6). Epub 2022 Jun 8.

Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

In inborn errors of metabolism, such as amino acid breakdown disorders, loss of function mutations in metabolic enzymes within the catabolism pathway lead to an accumulation of the catabolic intermediate that is the substrate of the mutated enzyme. In patients of such disorders, dietarily restricting the amino acid(s) to prevent the formation of these catabolic intermediates has a therapeutic or even entirely preventative effect. This demonstrates that the pathology is due to a toxic accumulation of enzyme substrates rather than the loss of downstream products. Read More

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Setting Sun Ectopia Lentis in Homocystinuria.

Ophthalmic Surg Lasers Imaging Retina 2022 06 1;53(6):354-355. Epub 2022 Jun 1.

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Detection of IEMs by Mass Spectrometry Techniques in High-Risk Children: A Pilot Study.

Indian J Pediatr 2022 Jun 17. Epub 2022 Jun 17.

Pediatric Biochemistry Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Objectives: To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques.

Methods: Children considered high-risk for IEM were screened for metabolic diseases during a 3-y period. Dried blood spots and urine samples were analyzed by tandem mass spectrometry (LC-MS/MS) and gas chromatograph-mass spectrometry (GCMS). Read More

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Homocysteine Metabolism Pathway Is Involved in the Control of Glucose Homeostasis: A Cystathionine Beta Synthase Deficiency Study in Mouse.

Cells 2022 05 25;11(11). Epub 2022 May 25.

Unité de Biologie Fonctionnelle et Adaptative, Université Paris Cité, CNRS, 75013 Paris, France.

Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. Read More

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[Clinical characteristics and CBS gene analysis of 13 cases with classic homocystinuria].

Zhonghua Er Ke Za Zhi 2022 Jun;60(6):533-538

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored. The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children's Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively. There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. Read More

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Investigation on a MMACHC mutant from cblC disease: The c.394C>T variant.

Biochim Biophys Acta Proteins Proteom 2022 Jun 23;1870(6):140793. Epub 2022 May 23.

Biophysics Institute, National Research Council, Palermo 90143, Italy. Electronic address:

The cblC disease is an inborn disorder of the vitamin B12 (cobalamin, Cbl) metabolism characterized by methylmalonic aciduria and homocystinuria. The clinical consequences of this disease are devastating and, even when early treated with current therapies, the affected children manifest symptoms involving vision, growth, and learning. The illness is caused by mutations in the gene codifying for MMACHC, a 282aa protein that transports and transforms the different Cbl forms. Read More

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Isolated psychiatric presentation of cobalamin C type disorder with novel mutation in middle childhood: A case report.

Asian J Psychiatr 2022 Jul 25;73:103131. Epub 2022 Apr 25.

Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. 249201. Electronic address:

A 9-year-old boy presented with abnormal behavior for six months. He had unprovoked aggressive behavior, and occasional self-inflicting behavior. He also had decreased appetite, anhedonia, apathy, reduced sleep, low energy, motivation, and poor interaction with parents and peers. Read More

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Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency.

J Inherit Metab Dis 2022 Apr 23. Epub 2022 Apr 23.

Department of Pediatrics, Reference Center for Inborn Error of Metabolism, Necker and Robert-Debré Hospital, APHP, Université Paris Cité, Paris, France.

MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early-onset patients mostly exhibit a life-threatening acute neurologic deterioration. Furthermore, data on early-onset patients' long-term outcomes are scarce. Read More

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Epimutations in both the TESK2 and MMACHC promoters in the Epi-cblC inherited disorder of intracellular metabolism of vitamin B.

Clin Epigenetics 2022 04 19;14(1):52. Epub 2022 Apr 19.

INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, University of Lorraine, 9 Avenue de la Forêt de Haye, 54000, Nancy, France.

Background: epi-cblC is a recently discovered inherited disorder of intracellular vitamin B metabolism associating hematological, neurological, and cardiometabolic outcomes. It is produced by an epimutation at the promoter common to CCDC163P and MMACHC, which results from an aberrant antisense transcription due to splicing mutations in the antisense PRDX1 gene neighboring MMACHC. We studied whether the aberrant transcription produced a second epimutation by encompassing the CpG island of the TESK2 gene neighboring CCDC163P. Read More

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The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China.

Taiwan J Obstet Gynecol 2022 Mar;61(2):290-298

The First Affiliated Hospital of Zhengzhou University, Genetic and Prenatal Diagnosis Center, No.1 Jianshe East Road, Zhengzhou, Henan, CN 450052, China. Electronic address:

Objectives: To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees.

Materials And Methods: Gene analyses were performed for 244 pedigrees. There are 130 pedigrees, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis. Read More

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Postauthorization safety study of betaine anhydrous.

J Inherit Metab Dis 2022 Mar 31. Epub 2022 Mar 31.

Division of Child Neurology and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital, Heidelberg, Germany.

Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Read More

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A case series of cerebral venous thrombosis as the first manifestation of homocystinuria.

Eur Stroke J 2021 Dec 12;6(4):420-427. Epub 2021 Nov 12.

Department of Inherited Metabolic Disorders, Queen Elizabeth Hospital Birmingham, Birmingham, UK.

Background: Cerebral venous thrombosis (CVT) is an important cause of stroke particularly in younger patients and potentially fatal if diagnosis is delayed. The presentation of symptoms is highly variable and consequently the diagnosis and underlying cause is often delayed or overlooked. Homocystinuria, a rare autosomal recessive disorder is an identified risk factor for CVT. Read More

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December 2021

Inherited defects of cobalamin metabolism.

Vitam Horm 2022 21;119:355-376. Epub 2022 Feb 21.

Department of Human Genetics, McGill University, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Cobalamin (vitamin B) is required for activity of the enzymes methylmalonyl-CoA mutase and methionine synthase in human cells. Inborn errors affecting cobalamin uptake or metabolism are characterized by accumulation of the substrates for these enzymes, methylmalonic acid and homocysteine, in blood and urine. Inborn errors affecting synthesis of the adenosylcobalamin coenzyme required by methylmalonyl-CoA mutase (cblA and cblB) result in isolated methylmalonic aciduria; inborn errors affecting synthesis of the methylcobalamin coenzyme required by methionine synthase (cblE and cblG) result in isolated homocystinuria. Read More

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Intracellular processing of vitamin B by MMACHC (CblC).

Vitam Horm 2022 15;119:275-298. Epub 2022 Mar 15.

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States.

Vitamin B (cobalamin, Cbl, B) is a water-soluble micronutrient synthesized exclusively by a group of microorganisms. Human beings are unable to make B and thus obtain the vitamin via intake of animal products, fermented plant-based foods or supplements. Vitamin B obtained from the diet comprises three major chemical forms, namely hydroxocobalamin (HOCbl), methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Read More

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Homozygous whole body Cbs knockout in adult mice features minimal pathology during ageing despite severe homocysteinemia.

FASEB J 2022 04;36(4):e22260

Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Deficiencies in Cystathionine-β-synthase (CBS) lead to hyperhomocysteinemia (HHCy), which is considered a risk factor for cardiovascular, bone and neurological disease. Moreover, CBS is important for the production of cysteine, hydrogen sulfide (H S) and glutathione. Studying the biological role of CBS in adult mice has been severely hampered by embryological disturbances and perinatal mortality. Read More

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Diagnosis of inborn errors of metabolism within the expanded newborn screening in the Madrid region.

JIMD Rep 2022 Mar 27;63(2):146-161. Epub 2022 Jan 27.

Sección de Gastroenterología y Nutrición Hospital Infantil Universitario Niño Jesús Madrid Spain.

We present the results of our experience in the diagnosis of inborn errors of metabolism (IEM) since the Expanded Newborn Screening was implemented in our Region. Dried blood samples were collected 48 h after birth. Amino acids and acylcarnitines were quantitated by mass spectrometry (MS)/MS. Read More

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Different Pattern of Cardiovascular Impairment in Methylmalonic Acidaemia Subtypes.

Front Pediatr 2022 23;10:810495. Epub 2022 Feb 23.

Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Methylmalonic acidaemia (MMA) has been reported to be associated with cardiovascular involvement, especially for the combined type with homocystinuria. We have screened 80 control subjects and 99 MMA patients (23 isolated type and 76 combined type) using electrocardiograph and echocardiography. 32 cases (34%) of ECG changes were found including sinus tachycardia ( = 11), prolonged QTc interval ( = 1), I-degree atrioventricular block ( = 1), left axis deviation ( = 5) and T wave change ( = 14). Read More

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February 2022

The Follow-Up of Chinese Patients in cblC Type Methylmalonic Acidemia Identified Through Expanded Newborn Screening.

Front Genet 2022 15;13:805599. Epub 2022 Feb 15.

Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The cblC type of combined methylmalonic acidemia and homocystinuria, an inherited disorder with variable phenotypes, is included in newborn screening (NBS) programs at multiple newborn screening centers in China. The present study aimed to investigate the long-term clinical benefits of screening individual. A national, retrospective multi-center study of infants with confirmed cblC defect identified by NBS between 2004 and 2020 was conducted. Read More

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February 2022

Cranial Magnetic Resonance Imaging Findings in Hypotonic Infants with Cobalamin Deficiency and Combined Methylmalonic Aciduria and Homocystinuria.

Klin Padiatr 2022 Mar 24;234(2):105-112. Epub 2022 Feb 24.

Radiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.

Vitamin B12 begins to accumulate in infants within the first six months while mothers often remain asymptomatic and infantile vitamin B12 deficiency may not be noticed until the onset of neurological effects. In infants with Cbl deficiency, long-term exposure to elevated methylmalonic acid and homocysteine (MMA-HC) may have toxic effects on the central nervous system. The aim of this study was to evaluate cranial magnetic resonance (MRI) findings of 23 hypotonic infants that were followed up with a diagnosis of nutritional Cbl deficiency and combined MMA-HC. Read More

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High Myopia: A Pointer of an Inborn Error of Metabolism.

Cureus 2022 Jan 4;14(1):e20930. Epub 2022 Jan 4.

Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, IND.

An 11-year-old boy with marfanoid habitus and high myopia presented with multiple episodes of seizures. He was found to have arachnodactyly, hypermobile joints, ectopia lentis, cerebral venous sinus thrombosis (CVST) with very high serum methionine and homocysteine. Genetic evaluation unveiled homocystinuria due to cystathionine beta-synthase deficiency. Read More

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January 2022

Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists.

Orphanet J Rare Dis 2022 02 2;17(1):33. Epub 2022 Feb 2.

Department of Pediatrics, Città della Salute e della Scienza University Hospital, University of Torino, Piazza Polonia 94, 10126, Turin, Italy.

Background: Methylmalonic aciduria and homocystinuria, CblC type (OMIM #277400) is the most common disorder of cobalamin intracellular metabolism, an autosomal recessive disease, whose biochemical hallmarks are hyperhomocysteinemia, methylmalonic aciduria and low plasma methionine. Despite being a well-recognized disease for pediatricians, there is scarce awareness of its adult presentation. A thorough analysis and discussion of cobalamin C defect presentation in adult patients has never been extensively performed. Read More

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February 2022

Neurodevelopmental and neuropsychiatric disorders in cobalamin C disease: a case report and review of the literature.

Cold Spring Harb Mol Case Stud 2022 02 24;8(2). Epub 2022 Mar 24.

Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, California 92093, USA.

Cobalamin C disease is the most common complementation class of cobalamin disorders. Here, we present a case of a 14-yr-old male with early-onset cblC disease and autism spectrum disorder (ASD) admitted to our inpatient medical service for behavioral decompensation. We use this case to highlight key aspects of the neurodevelopmental and neuropsychiatric disorders associated with cblC disease. Read More

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February 2022

Newborn Screening in Japan-2021.

Toshihiro Tajima

Int J Neonatal Screen 2022 Jan 4;8(1). Epub 2022 Jan 4.

Jichi Children's Medical Center Tochigi, Jichi Medical University, Shimotsuke-shi 329-0498, Japan.

Japan's Newborn Mass Screening (NBS) was started in 1977 for amino acid metabolism disorders (phenylketonuria (PKU), homocystinuria, maple syrup urine, histidineemia (discontinued in 1993)) and galactosemia at the national level as a national project [... Read More

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January 2022

The QChip1 knowledgebase and microarray for precision medicine in Qatar.

NPJ Genom Med 2022 Jan 19;7(1). Epub 2022 Jan 19.

Department of Genetic Medicine, Weill Cornell Medicine, New York, NY, USA.

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 10 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs. Read More

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January 2022

Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.

Nat Commun 2022 01 10;13(1):134. Epub 2022 Jan 10.

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. Read More

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January 2022

A Glance into MTHFR Deficiency at a Molecular Level.

Int J Mol Sci 2021 Dec 23;23(1). Epub 2021 Dec 23.

Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.

MTHFR deficiency still deserves an investigation to associate the phenotype to protein structure variations. To this aim, considering the MTHFR wild type protein structure, with a catalytic and a regulatory domain and taking advantage of state-of-the-art computational tools, we explore the properties of 72 missense variations known to be disease associated. By computing the thermodynamic ΔΔG change according to a consensus method that we recently introduced, we find that 61% of the disease-related variations destabilize the protein, are present both in the catalytic and regulatory domain and correspond to known biochemical deficiencies. Read More

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December 2021

Stroke and stroke-like episodes in inborn errors of metabolism: Pathophysiological and clinical implications.

Mol Genet Metab 2022 01 23;135(1):3-14. Epub 2021 Dec 23.

Child Neurology and Psychiatry Unit - Department of Human Neuroscience-Sapienza, Università di Roma, Italy. Electronic address:

Inborn errors of metabolism causing stroke (ischemic or haemorrhagic) or stroke-like episodes (e.g., that are also called "metabolic strokes" and include acute brain lesions not related with alterations of blood flow) cover a wide range of diseases in which acute metabolic decompensations after trigger events (e. Read More

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January 2022

Hypoventilation and progressive encephalopathy in a neonate with MTHFR deficiency.

BMJ Case Rep 2022 Jan 4;15(1). Epub 2022 Jan 4.

Neonatology, Rainbow Children's Hospital, Hyderabad, Telangana, India.

Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive inherited inborn error of metabolism, which presents with various severity depending on the level of residual enzyme activity. In neonates, it can present with recurrent hypoventilation episodes, persistent encephalopathy with or without microcephaly. MTHFR deficiency also results in hyperhomocysteinemia, homocystinuria and hypomethionemia. Read More

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January 2022

Characterization and application of l-methionine γ-lyase Q349S mutant enzyme with an enhanced activity toward l-homocysteine.

J Biosci Bioeng 2022 Mar 23;133(3):213-221. Epub 2021 Dec 23.

Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan. Electronic address:

l-Methionine γ-lyse (MGL), a pyridoxal 5'-phosphate-dependent enzyme, catalyzes the α,γ-elimination of l-methionine (l-Met) and l-homocysteine (l-Hcy) to produce α-keto acids, thiols, and ammonia. Previously, various mutant enzymes of Pseudomonas putida MGL (PpMGL) were prepared to identify a homocysteine (Hcy)-specific enzyme that would assist the diagnosis of homocystinuria. Among the mutat enzymes the Q349S mutant exhibited high degradation activity toward l-Hcy. Read More

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