Abstract

Nine patients with homocystinuria due to cystathionine synthase deficiency were treated with pyridoxine: 6 responded biochemically and 5 of these showed marked clinical improvement. Full biochemical response was only obtained slowly in some patients. Response occurred in those patients who were least severely affected by their disease and was consistent within families. No patient experienced a thrombotic episode during pyridoxine treatment. Pretreatment serum and red cell folate levels were normal. All patients showed lowering of folate levels while receiving pyridoxine, and administration of folic acid caused further biochemical improvement in pyridoxine responsive patients and subjective clinical improvement in all. The mechanism for lowering of folate levels during pyridoxine administration may depend upon removal of substrate inhibition of the enzyme N⁵ methyltetrahydrofolate homocysteine methyl transferase, due to pyridoxine-induced lowering of the substrate homocysteine. It is suggested that patients with homocystinuria should be given a long trial with pyridoxine and that folic acid should be given in all cases where pyridoxine is used.