Summary. Deficiency in methylenetetrahydrofolate reductase (MTHFR), the enzyme involved in the remethylation of homocysteine to methionine using methyltetrahydrofolate as cofactor, induces hyperhomocysteinaemia, homocysteinuria, hypomethioninaemia and low methylfolate levels. Diagnosis usually occurs during infancy because of various neurological abnormalities. We report MTHFR deficiency diagnosed in an adult woman after a pulmonary embolism. Her adult sister, intellectually retarded, suffered from the same disease. Molecular analysis of the MTHFR gene exhibited four different mutations (two missense mutations, one exon skipping and C677T). The impact of these mutations was analysed through the biological abnormalities in the parents and children.Keywords: hyperhomocysteinaemia, pulmonary embolism, MTHFR deficiency, molecular analysis, methylfolate.Among the risk factors of thrombophilia, hyperhomocysteinaemia is responsible for venous and arterial thrombotic diseases (Welch & Loscalzo, 1998).Elevation of plasma homocysteine results from inherited or nutritional factors. Severe hyperhomocysteinaemia is due to enzyme deficiencies. Cystathionine b-synthase, present on the trans-sulphuration pathway, changes homocysteine to cystathionine, by using vitamin B 6 as coenzyme, and is associated with precocious vascular disease. Methylenetetrahydrofolate reductase (MTHFR) catalyses the synthesis of 5-methyltetrahydrofolate, the methyl donor for the vitamin B 12 -dependent remethylation of homocysteine to methionine via methionine synthase (Rosenblatt, 2001). Among various mutations on the MTHFR gene, a thermolabile variant caused by a point mutation in exon 4 of the gene (C677fiT) (AlafiVal) usually induces mild hyperhomocysteinaemia, moderate decreased MTHFR activity and decreased folate status . Nutritional deficiency in the vitamin cofactors (folate, vitamin B 12 and vitamin B 6 ) required for homocysteine metabolism may promote hyperhomocysteinaemia.We report a case of severe pulmonary embolism in a young adult taking oral contraceptives without any known factor of thrombophilia, in whom hyperhomocysteinaemia and hypomethioninaemia related to severe MTHFR deficiency were found. Genetic studies of the family identified three mutations on the MTHFR gene, two of them novel and the C677fiT mutation. The impact of these mutations is discussed.
CASE REPORTThe patient, an obese 27-year-old woman, developed dyspnoea 8 months after taking oral contraceptives. One year before, she delivered a healthy child after a normal pregnancy. Since her childhood, she had walking problems, and she encountered difficulties at school. Neurological examination revealed bilateral Babinski signs. Helical computerized tomography showed bilateral pulmonary embolism and duplex ultrasonography revealed left iliac vein thrombosis. When factors associated with thrombophilia (blood levels of antithrombin, protein C, protein S, antiphospholipid antibodies, lupus anticoagulant, analysis of factor V Leiden and prothrombin G20210) were screened, no abnor...