MTHFR thermolabile variant에 대한 동형 접합자에서 조발 뇌졸중을 일으키는 선천적 MTHFR 결핍
Congenital MTHFR deficiency causing early-onset cerebral stroke in a case homozygous for MTHFR thermolabile variant
Abstract
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. In silico analysis using SIFT (http://blocks.fhcrc.org/sift/SIFT.html) and Polyphen (http://genetics.bwh.harvard.edu/pph2/) predicted that these variants were pathogenic. Under the diagnosis of MTHFR deficiency, the patient was managed with betaine, hydroxyl-cobalamin, and folate, which decreased his homocysteine level. He has not experienced a recurrent stroke-like episode during the 7 year ’ s follow-up period since the initial event of cerebral infarction. This is the first report of MTHFR deficiency in a Korean patient, and one of only a few cases reported in East Asian countries. Our report emphasizes the importance of detailed investigation of the underlying cause of hyperhomocysteinemia for patient prognosis with appropriate management, even if the patient bears a homozygous MTHFR thermolabile variant.