Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deficiency of methylenetetrahydrofolate reductase (MTHFR) is associated with a variable phenotype that includes mental retardation, gait abnormalities, and seizures. Many of the same clinical findings are also seen in patients with Angelman syndrome. We report on a patient with MTHFR deficiency who was initially diagnosed as having Angelman syndrome. This case illustrates that MTHFR deficiency can mimic the phenotype of Angelman syndrome and that MTHFR deficiency should be excluded in patients with manifestations of Angelman syndrome whose molecular studies of chromosome 15 are normal.
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PMID:Methylenetetrahydrofolate reductase deficiency in a patient with phenotypic findings of Angelman syndrome. 960 86

Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is an inborn error of folate metabolism, and is inherited as an autosomal recessive trait. MTHFR is a key enzyme in folate-dependent remethylation of homocysteine, and reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. Patients with this severe enzymatic deficiency are biochemically characterised by homocystinuria and hypomethioninaemia, and may suffer from neurological abnormalities, mental retardation and premature vascular disease. Here we report the molecular basis of severe MTHFR deficiency in four unrelated families from Turkish/Greek ancestry. By use of reverse-transcriptase (RT)-PCR, subsequently followed by direct sequencing analysis, we were able to identify four novel mutations in the MTHFR gene: two missense (983A-->G; 1027T-->G) and two nonsense (1084C-->T; 1711C-->T) mutations. Furthermore, a splice variant containing a premature termination codon, was observed in one patient, probably as a secondary effect of the 1027T-->G missense mutation. The ongoing identification and characterisation of mutations in the MTHFR gene will provide further insight into the heterogeneity of the clinical phenotype in severe MTHFR deficiency.
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PMID:Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. 978 Oct 30

Homocysteine is a sulphur-containing amino acid that is derived primarily from protein of animal origin. Classical homocystinuria is an inherited metabolic disorder that arises from defects in either the re-methylation or trans-sulphuration pathways of homocysteine metabolism and leads to skeletal abnormalities, mental retardation and a high risk of vascular disease. In contrast, moderate hyperhomocysteinaemia is associated with an increased risk of both arterial and venous thrombotic disease but no other abnormalities. This increased risk appears to be independent of other conventional risk factors. Many cases of hyperhomocysteineaemia have been attributed to defects in the enzyme cystathionine-beta-synthase (CBS) but this accounts for less than 1.5% of cases. A thermolabile variant of the enzyme methylenetetrahydrofolate reductase (MTHFR) arises from a C --> T transition at nucleotide 677 in the MTHFR gene resulting in an alanine-to-valine substitution. While the mutation does not appear to be associated with an increased risk of vascular disease, it results in excessively high homocysteine levels in response to a low or low-normal serum folate. Supplementation of the diet with folate, B6 and B12 can reduce homocysteine levels and this is the mainstay of treatment. Supplementation of grain with folate is undertaken in the USA to reduce the risk of neural tube defects in pregnant women. However, by reducing plasma homocysteine levels, it is estimated that this will save up to 50,000 lives per annum.
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PMID:Hyperhomocysteinaemia. 1085 81

Although genetic, nutritional, and environmental factors have been found to aggravate mental retardation in approximately 1% of individuals, no cause is known till date. In this study, two genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), C677T (rs#1801133) and A1298C (rs#1801131), have been investigated in idiopathic mental retardation (IMR) subjects. Significantly higher frequency of the C677 allele was observed in IMR (n = 155; chi(2) = 5.5; P = 0.019) and moderate IMR (n = 67; chi(2) = 6.16; P = 0.013) groups as compared to controls (n = 126); for A1298C, no significant difference was noticed. TDT analysis revealed preferential transmission of C677 allele to a small group of mild IMR probands (chi(2) = 5.545; P = 0.018). Higher frequency of CA haplotype was also noticed in IMR cases as compared to controls (chi(2) = 6.28; P = 0.012). We infer from the present investigation that these polymorphisms are not contributing to the aetiology of IMR in this population since both case-control and family-based analysis revealed no significant transmission of the mutated allele.
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PMID:Screening for methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Indian patients with idiopathic mental retardation. 1851 Jul 99

Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR), the very rare methionine synthase reductase (CblE) and methionine synthase (CblG) defects, and the recently identified CblD-variant-1 defect are primary remethylation defects characterized by an isolated defect in methionine synthesis without methylmalonic aciduria. The clinical signs are mainly neurological, and hematological signs are seen in CblE, CblG, and CblD-variant-1 defects. Patients with neonatal or early-onset disease exhibit acute neurological distress. Infants and children have unspecific mental retardation, often with acquired microcephaly. Without appropriate therapy, they may experience acute or rapidly progressive neurological deterioration, which may be fatal. Adolescents and adults show normal development or mild developmental delay initially and then experience rapid neurological or behavioral deterioration. A few patients may have signs of subacute combined degeneration of the spinal cord. Adults may be asymptomatic or present with isolated thromboembolism. All patients with suspected remethylation disorders should receive emergency treatment with parenteral administration of hydroxocobalamin and folate supplements combined with betaine orally. The long-term treatment of CblE, CblG, and CblD-variant-1 defects consists of parenterally administered hydroxocobalamin and orally administered folate and betaine supplements, whereas patients with MTHFR deficiency require long-term oral folate and betaine supplements. Long-term oral methionine therapy should also be considered. Early treatment may lead to a favorable outcome with developmental recovery and prevention of further neurological deterioration. In contrast, most late-treated patients have severe and irreversible neuromotor impairments. Hematological abnormalities are easily corrected.
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PMID:Isolated remethylation disorders: do our treatments benefit patients? 2049 Sep 23

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been suggested as being associated with cerebral palsy (CP) but the evidence is uncertain. The purpose of this study was to investigate whether MTHFR gene polymorphisms contribute to the development of CP in Chinese infants. For this study, 169 health controls and 159 infants with CP including 43 cases also suffering from mental retardation (MR) were recruited. Genomic DNA was prepared from venous blood and all five single nucleotide polymorphisms in MTHFR (rs4846049, rs1476413, rs1801131, rs1801133 and rs9651118) were genotyped using TaqMan technology. There were no significant differences in allele or genotype frequencies between the CP patients and controls at any of the five genetic polymorphisms. Subgroup analysis found statistically significant difference in allele and genotype frequencies between cases with both CP and MR (CP + MR) compared with both CP-only cases and controls at rs4846049, rs1476413 and rs1801131. The frequencies of the T alleles of rs4846049, rs1476413 and the G allele of rs1801131 were greater in the CP + MR patients than in the CP-only patients and controls. This study provides the first evidence pointing to a MTHFR gene polymorphism as a potential risk factor for CP combined with MR.
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PMID:Methylenetetrahydrofolate reductase gene polymorphisms and cerebral palsy in Chinese infants. 2096 91