Hyperhomocysteinemia is a risk factor for early-onset venous thrombosis. It can be caused by genetic defects in methionine-homocysteine metabolism. The thermolabile variant of methylene-tetrahydrofolate reductase (MTHFR), c.677C>T, is one of the most common genetic condition, which has been associated with mild to moderate hyperhomocysteinemia, and carriers of this variant are at increased risk of an early-onset stroke-like episode. However, congenital MTHFR deficiency is a rare inborn error of folate metabolism, causing marked hyperhomocysteinemia, and its combination with the thermolabile variant is rarely reported. In this report, we describe a young adult with cerebral infarction. The patient was homozygous for the MTHFR thermolabile variant, but markedly elevated hyperhomocysteinemia led us to investigate the whole MTHFR gene, which revealed two novel MTHFR mutations. This is the first report of MTHFR deficiency in a Korean patient, and one of only a few cases reported in East Asian countries. Despite its rarity, our report underlines the importance of its identification in hyperhomocysteinemia for patient prognosis with appropriate management.
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