Vitamin B-12 and liver activity and expression of methionine synthase are decreased in fetuses with neural tube defects.

Background: The risk of neural tube defects (NTDs) is influenced by nutritional factors and genetic determinants of one-carbon metabolism. A key pathway of this metabolism is the vitamin B-12- and folate-dependent remethylation of homocysteine, which depends on methionine synthase (MS, encoded by MTR), methionine synthase reductase, and methylenetetrahydrofolate reductase. Methionine, the product of this pathway, is the direct precursor of S-adenosylmethionine (SAM), the universal methyl donor needed for epigenetic mechanisms.

Fumonisin FB1 treatment acts synergistically with methyl donor deficiency during rat pregnancy to produce alterations of H3- and H4-histone methylation patterns in fetuses.

Scope: Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl-deficient diet (MDD) and fumonisin FB1 are risk factors for neural tube defects and cancers. Evidence indicates that FB1 impairs folate metabolism.

A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma.

The remethylation of homocyteine into methionine is catalyzed either by methionine synthase (MTR) or by betaine-homocysteine methyltransferase (BHMT), in the liver. Choline/betaine deficiency and impaired BHMT pathway have been associated with hepatocellular carcinogenesis, in animal models. The molecular mechanisms that impair the BHMT pathway are unknown.

Ovarian tissue cryopreservation and subsequent spontaneous pregnancies in a patient with classic galactosemia.

Objective: To report two consecutive spontaneous pregnancies in a compound heterozygous patient with classic galactosemia and a heterozygous partner, 6 years after ovarian tissue cryopreservation.

Design: Case report.

Setting: Tertiary health care center.

Life-threatening methylenetetrahydrofolate reductase (MTHFR) deficiency with extremely early onset: characterization of two novel mutations in compound heterozygous patients.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzymatic component of the folate cycle, converting 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine into methionine. Severe MTHFR deficiency is a rare recessive disease leading to major hyperhomocysteinemia, homocystinuria, and progressive neurological distress within the two first decades of life. More than 50 mutations have been reported so far in affected patients but only a few cases with very early onset of symptoms during the first weeks have been described, most of them showing a particular severe clinical course.