Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.
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PMID:Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia. 2679 54

Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction. In this study, we report 4 patients from 2 unrelated families, with confirmed diagnosis of TC deficiency. Patients initially had a typical presentation of TC deficiency: severe diarrhea and vomiting, recurrent infections, stomatitis, macrocytic anemia, and neutropenia. Interestingly one of the patients was diagnosed at 3 months of age and developed ataxic gait related to cerebellar atrophy at the age of 14 months. His elder affected sibling was diagnosed at 5 months of age was completely normal. Two sibs, diagnosed at 2 months of age and immediately after birth, had autism spectrum disorder. Molecular investigations showed 2 novel mutations in TCN2 gene. Patients were treated and stayed stable on weekly injection of Cbl. In conclusion, TC deficiency has a wide heterogeneity in clinical phenotype, genotype, laboratory, and radiologic findings. Early detection of the disease and early initiation of aggressive parenteral treatment is probably associated with better prognosis and disease control.
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PMID:Long-term Outcome of 4 Patients With Transcobalamin Deficiency Caused by 2 Novel TCN2 Mutations. 2853 14