Cystathionine β-synthase deficiency: Effects, of betaine supplementation after methioninie restriction in B6-nonresponsive homocystinuria

Purpose: For treatment of cystathionine β-synthase (CβS) deficiency, we determined the effect of betaine (N,N,N-trimethylglycine) therapy and examined the genotype-phenotype relationships to betaine. Methods: In five patients with B6-nonresponsive homocystinuria, we defined the CβS genotypes and determined metabolic responses to betaine as an additive to traditional dietary methionine restriction. Results: After betaine therapy, tHcy declined (mean 47.4 μmol/L; range: -21.2 to -104.0 μmol/L; P = 0.02), whereas total plasma cysteine and methionine did not change. Plasma methionine/tHcy ratios increased by 5.45 (range: +1.5 to 15.3; P = 0.05) inpatients with B6-nonresponsive alleles. Conclusion: Betaine improves metabolic control in B6-nonresponsive patients with homocystinuria after optimum dietary control.