Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 24 day old girl with homocystinuria and hypomethioninaemia caused by methylenetetrahydrofolate reductase deficiency presented with rapidly progressing encephalopathy and myopathy. An almost complete recovery was achieved by treatment with betaine.
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PMID:Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reductase deficiency. 262 32

We previously described demyelination in the brain and subacute combined degeneration of the spinal cord in a patient with 5,10-methylenetetrahydrofolate reductase deficiency. To assess the role of methionine, S-adenosylmethionine, folate, and neurotransmitter amine metabolism in the demyelination process, we measured these metabolites in CSF from this patient; the findings are compared with those obtained from three patients in whom neurologic deterioration had been halted by the administration of betaine. Folate concentrations were low, and amine and biopterin metabolism were abnormal in all patients. Methionine and S-adenosylmethionine concentrations were undetectable in the first patient. In those receiving betaine, methionine concentrations were proportional to the dose administered and S-adenosylmethionine concentrations were near normal. The results provide the first evidence for an association between defective S-adenosylmethionine metabolism and demyelination in humans.
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PMID:Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. 334 50

Two routes for the methylation of homocysteine to methionine, depending either on betaine or folate cofactor as methyl donor, were studied in liver and kidneys of normal and Ehrlich ascites carcinoma-bearing mice at various stages of their postnatal development. Distinct age-dependence in the activities of betaine methyltransferase, methylenetetrahydrofolate reductase and methionine synthase were found both in normal and tumour-bearing mice. Independent of the levels of enzyme activity in healthy mice, the tumour activated one route of methionine formation only, namely that utilizing methyltetrahydrofolate as the methyl donor. This effect was observed in host liver exclusively. No host age-related changes were found in Ehrlich ascites carcinoma growth.
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PMID:Age- and tumour-related changes in methionine biosynthesis in mice. 375 47

In a 3-year-old mentally retarded girl with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency among different therapeutic approaches only treatment with betaine (15-20 g/day) resulted in a satisfactory biochemical response. Betaine improved homocysteine remethylation and thus lowered plasma homocystine to trace amounts and normalized the previously very low plasma methionine concentration. This biochemical response was associated with a clinical improvement although she remained mentally retarded.
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PMID:Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. 638 Oct 59

A 16-year-old Japanese girl with 5,10-methylenetetrahydrofolate reductase deficiency showed peripheral neuropathy. There were no significant responses to vitamin B6, vitamin B12 or folate, given alone or in combination. With the addition of betaine monohydrate, she has been free from gait disturbance and muscle weakness. The concentration of S-adenosylmethionine in cerebrospinal fluid, which was undetectable before receiving betaine monohydrate, increased to about the normal level 24 months after treatment with betaine monohydrate.
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PMID:Effect of betaine on S-adenosylmethionine levels in the cerebrospinal fluid in a patient with methylenetetrahydrofolate reductase deficiency and peripheral neuropathy. 783 62

Hyperhomocyst(e)inemia (HCY) is caused either by genetic or nongenetic defect(s), and the clinical severity of HCY is correlated with the biochemical abnormality. Treatment of HCY is approached on the basis of its etiology and severity of defect. The preferred method of treatment for genetic HCY is activation of mutant enzyme activity with the cofactor or the precursor of cofactor. If HCY does not respond to this treatment, pharmacological doses of betaine or folic acid should be used to enhance the alternative pathway of homocysteine turnover. Phenotypic expression of minor genetic defects, such as heterozygous cystathionine synthase deficiency and thermolabile methylenetetrahydrofolate reductase (MTHFR) can be amplified or masked by nongenetic (nutritional) factor(s). Hence, supplementation of folic acid, vitamin B-12, pyridoxine and choline to maintain their serum concentrations above low normal range may satisfactorily prevent the development of moderate HCY due to a minor genetic defect.
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PMID:Treatment of hyperhomocyst(e)inemia: physiological basis. 864 69

A girl aged 7.5 years with deficiency of 5,10-methylenetetrahydrofolate reductase was treated from early infancy with betaine, 3-6 g daily. She has slight microcephaly, moderate developmental delay, and impaired vision but there have been no obvious signs of folate deficiency. From 4 years of age, she developed an unexplained extreme increase in appetite and weight. Recent magnetic resonance imaging of her brain was normal. The plasma methionine levels have been normal but in the lower range, and the total plasma homocysteine concentrations have been moderately increased (54 to 85 mumol/l) without obvious correlation with the different betaine doses given. Folic acid has sometimes been added.
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PMID:Long term treatment with betaine in methylenetetrahydrofolate reductase deficiency. 878 31

MR imaging showed severe atrophy and large areas without myelination in the brain of a girl with methylenetetrahydrofolate reductase deficiency. Proton MR spectroscopy revealed mild signal reduction of N-acetylaspartate. After treatment with betaine, a second MR imaging study revealed a decrease in the size of the hypomyelinated zones that was paralleled by improved clinical status and laboratory findings.
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PMID:MR and proton MR spectroscopy of the brain in hyperhomocysteinemia caused by methylenetetrahydrofolate reductase deficiency. 909 Apr 18

The sulfur-containing amino acid, homocysteine, is formed from the essential amino acid methionine, and a number of B vitamins are involved in methionine metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine beta synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the transsulfuration pathway and the urinary excretion of sulfur. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocyst(e)ine elevation, as does diminished renal function, both of which are common in the elderly. It is also established that homocyst(e)ine elevation of this order is associated with increased cardiovascular risk but is also associated with most established risk factors, although it is thought to be an independent contributor. In the inborn error of metabolism homocystinuria due to cystathionine beta synthase deficiency there is greatly increased circulating homocyst(e)ine and a clear association with precocious vascular disease. In about 50% of these patients there is a vascular event before the age of 30 years. The homocysteine-induced adverse vascular changes appear to result from endothelial and smooth muscle cell effects and increased thrombogenesis. We have documented a highly significant reduction in the occurrence of vascular events during 539 patient years of treatment in 32 patients with cystathionine beta synthase deficiency (mean age 30 years, range 9-66 years) by aggressive homocyst(e)ine lowering with pyridoxine, folic acid, and B12 (p = 0.0001). The 15 pyridoxine nonresponsive patients also received oral betaine. Although a cause and effect relationship is postulated for the increased cardiovascular risk associated with mild homocysteine elevation, a common cause of this elevation is the methylenetetrahydrofolate reductase C677T mutation. Homozygotes occur in about 11% of Caucasian populations. However, the mutation is not associated with increased coronary risk. Since mild homocysteine elevation is easily normalized by B vitamin supplementation, usually with folic acid, it remains for controlled clinical trials of this inexpensive therapy to determine whether normalizing mild homocyst(e)ine elevation reduces cardiovascular risk.
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PMID:B vitamins and homocysteine in cardiovascular disease and aging. 992 44

The cases of three infants, two Saudi and one Bahraini, with methylenetetrahydrofolate reductase (MTHFR) deficiency are reported. They presented in the neonatal period with lethargy, poor feeding, hypotonia, and frequent apneas. Tandem mass spectrometry (MS/MS) of a blood spot indicated very low methionine level and of urine revealed high homocysteine. The diagnosis was confirmed by demonstrating severe deficiency of MTHFR in the cultured skin fibroblast. All patients were treated with folinic acid, vitamin B12, betaine, and methionine, with good initial response to the therapy. In two patients, the diagnosis was late and their disease was severe, resulting in neurological crippling. However, in the third patient, who was diagnosed and treated early, the current neurological status is normal. In her case, at 1 month of age, the brain FDG PET scan documented very faint cerebral and cerebellar cortical activities. After 5 months of intensive therapy, that included 200-600 mg/kg per day methionine, she had a dramatic clinical and biochemical recovery as well as a parallel improvement in FDG PET. Brain MR spectroscopy indicated normal neuronal glial and myelin markers for her age. We conclude that the functional changes confirmed by the FDG PET study were better correlated with the clinical course of the patient and adequately monitored the response to therapy. This disease warrants early detection through neonatal screening program, since the beneficial effect of early administration of adequate therapy with combined use of betaine and a high dose of methionine is rewarding and may be the treatment of choice for MTHFR deficiency.
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PMID:Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography of the brain, MR spectroscopy, and therapeutic attempts in methylenetetrahydrofolate reductase deficiency. 1041 24


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