Methylenetetrahydrofolate reductase (MR) deficiency: Thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts

Rosenblatt, David S.; Lue-Shing, Helena; Arzoumanian, Artin; Low-Nang, L.; Matiaszuk, Nora

doi:10.1016/0885-4505(92)90029-x

Cited by 23 publications

(13 citation statements)

References 14 publications

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“…1) which forms DNA in sufficient amounts to prevent megaloblastic anaemia. Megaloblastic anaemia is infrequent in people with MR deficiency (Rosenblatt et al, 1992). Our patient was not anaemic and only moderately megaloblastic (macrocytotic).…”

Section: Discussionmentioning

confidence: 82%

“…In homozygotes with this variant, certain activity was reduced by approximately 50% in lymphocytes compared with normal activity and MR was typically thermolabile, with residual activity of less than 20% after heat inactivation. In another study, it appeared that the presence of a thermolabile reductase was associated with a later clinical presentation (Rosenblatt et al, 1992). Thermolability was not tested in our patient.…”

Section: Discussionmentioning

confidence: 89%

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Homocysteinemia and schizophrenia as a case of methylation deficiency

Regland

Johansson

Gottfries

1994

J. Neural Transmission

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A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for a diagnosis of schizophrenia and who was found to have a significantly increased serum level of homocysteine. Repeatedly, she improved on frequent cobalamin injections and deteriorated in periods without treatment. The effects of prolonged weekly treatment appeared to diminish as time went on, suggesting that the abnormality was not wholly cobalamin-dependent. It was found that methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts was reduced to a magnitude that is found among people with heterozygous deficiency. A defect in MR activity indicates a deficiency in methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation of homocysteine to methionine. Thus, reduced methylation may explain the increased levels of homocysteine and the transient effects of cobalamin treatment in the patient. Theoretically, MTHF should be the optimal treatment for her. The case reported highlights the importance of assessing the serum homocysteine level in order to detect methylation deficiency in patients with schizophrenia.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 89%

Homocysteinemia and schizophrenia as a case of methylation deficiency

Regland

Johansson

Gottfries

1994

J. Neural Transmission

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“…The next most common mutations are of the nonsense type: p.Arg183* (c.547C>T; 6 families), p.Glu470* (c.1408G>T; 6 families), and p.Arg567* (c.1699C>T; 5 families). Fibroblasts from patients homozygous for p.Arg183* [Rosenblatt, et al., ; ; Goyette, et al., ; Burda, et al., 2015b] and p.Glu470* [Burda, et al., 2015b] have virtually undetectable MTHFR activity. Anomalously, a patient homozygous for p.Arg567* was reported to have residual activity in fibroblasts of between 20% and 50% of healthy controls ([Kluijtmans, et al., ], Supp.…”

Section: Variantsmentioning

confidence: 99%

Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency

et al. 2016

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Severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is caused by mutations in the MTHFR gene and results in hyperhomocysteinemia and varying severity of disease, ranging from neonatal lethal to adult onset. Including those described here, 109 MTHFR mutations have been reported in 171 families, consisting of 70 missense mutations, 17 that primarily affect splicing, 11 nonsense mutations, seven small deletions, two no-stop mutations, one small duplication, and one large duplication. Only 36% of mutations recur in unrelated families, indicating that most are "private." The most common mutation is c.1530A>G (numbered from NM_005957.4, p.Lys510 = ) causing a splicing defect, found in 13 families; the most common missense mutation is c.1129C>T (p.Arg377Cys) identified in 10 families. To increase disease understanding, we report enzymatic activity, detected mutations, and clinical onset information (early, <1 year; or late, >1 year) for all published patients available, demonstrating that patients with early onset have less residual enzyme activity than those presenting later. We also review animal models, diagnostic approaches, clinical presentations, and treatment options. This is the first large review of mutations in MTHFR, highlighting the wide spectrum of disease-causing mutations.

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“…The level of methylcobalamin was relatively low (Table II). Measurement of the activity of methylenetetrahydrofolate reductase in cultured fibroblasts confirmed that the patient was severely deficient with activity of 0.757 nmol of formaldehyde/(mg of protein и hr) (control range 13.3 ± 4.6) [Rosenblatt et al, 1979[Rosenblatt et al, , 1992Rosenblatt and Erbe, 1977].…”

Section: Clinical Reportmentioning

confidence: 99%

Methylenetetrahydrofolate reductase deficiency in a patient with phenotypic findings of Angelman syndrome

et al. 1998

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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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Methylenetetrahydrofolate reductase (MR) deficiency: Thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts

Cited by 23 publications

References 14 publications

Homocysteinemia and schizophrenia as a case of methylation deficiency

Homocysteinemia and schizophrenia as a case of methylation deficiency

Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency

Methylenetetrahydrofolate reductase deficiency in a patient with phenotypic findings of Angelman syndrome

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