REMETHYLATION DEFECTS - GUIDELINES FOR CLINICAL-DIAGNOSIS AND TREATMENT

The main remethylation defects include disorders which all have defect ive methionine synthesis in common. Methylenetetrahydrofolate reductas e deficiency impairs methyltetrahydrofolate synthesis, defects in cyto solic reduction of hydroxocobalamin (CblC/D) impair the synthesis of b oth methyl- and adenosyl cobalamin and deficiencies of methionine synt hase (CblE/G) are associated with defective methyl cobalamin synthesis . The clinical presentation is characterized by acute neurological dis tress in early infancy. In childhood, patients present with progressiv e encephalopathy with an end-stage which has many signs in common with the adult onset form. In fact, both have more or less severe signs of subacute degeneration of the cord. Cobalamin defective patients must be treated with parenteral supplementation of hydroxocobalamin (1-2 mg per dose). Some methylenetetrahydrofolate patients could be folate re sponsive and must have a high-dosage folate trial. In addition, oral b etaine supplementation (2-9 g per day depending on age) appears an eff ective means to prevent further neurological deterioration.