Limited effectiveness of betaine therapy for cystathionine beta synthase deficiency.

BACKGROUND: Orally administered betaine (Bet) is regarded as an effective and safe therapy for homocystin-uria. However, even when patients' serum Bet concentrations are increased by supplementation, serum homocysteine (Hcy) concentrations are often not lowered to the normal range. The present study tested the hypothesis that with relatively high serum methionine (Met), serum Hcy does not adequately decrease, even when serum Bet concentrations are potentially therapeutic.

METHODS: The present study examines the relationship between these amino acids by high-performance liquid chromatography (HPLC) in a total of 63 samples obtained over 2 years from two patients with cystathionine beta synthase (CBS) deficiency.

RESULTS: When serum Met was less than 80 micro mol/L (1.2 mg/dL), the treatment reduced serum Hcy to within the normal range. When serum Met exceeded 80 micro mol/L, serum Hcy showed only a limited decrease, despite sufficient doses of Bet (serum concentration, over 250 micro mol/L). The findings of the present study suggest that it is necessary to follow a low methionine diet that keeps serum Met within the normal range when treating patients with homocystinuria due to CBS deficiency when Bet is administered. Homocystinuria is a rare congenital metabolic disease and the data presented in the present paper, although it relates to only two patients, is worth reporting.