CEREBROSPINAL-FLUID AND PLASMA TOTAL HOMOCYSTEINE AND RELATED METABOLITES IN CHILDREN WITH CYSTATHIONINE BETA-SYNTHASE DEFICIENCY - THE EFFECT OF TREATMENT

The neurologic complications of cystathionine beta-synthase deficiency are thought to be secondary to accumulation of homocyst(e)ine in the CNS. Treatment of this disorder with betaine has been shown to improve the behavior of individuals, to reduce plasma total homocysteine, and to correct secondary abnormalities of serine. To test the hypothesis that homocyst(e)ine accumulates within the CNS and that this can be re duced by treatment with betaine, we measured total homocysteine and re lated metabolites in the plasma of 10 children with cystathionine beta -synthase deficiency and cerebrospinal fluid of five children before a nd during betaine therapy. In plasma, betaine significantly lowered to tal homocysteine (but not to the normal range) and had a variable effe ct on methionine. In the cerebrospinal fluid, total homocysteine was r aised before treatment (mean 1.2 mu M) and was significantly reduced b y betaine (mean 0.32 mu M) but not to the normal range (<0.10 mu M). C erebrospinal fluid methionine was raised before and during treatment, but betaine did not cause a significant further increase. Cerebrospina l fluid serine was significantly reduced before treatment and rose to the normal range with betaine. Cerebrospinal fluid S-adenosylmethionin e was normal before treatment and rose significantly with treatment; t here were no significant changes in cerebrospinal fluid 5-methyltetrah ydrofolate. The demonstration of accumulation of homocysteine within t he CNS lends support to the hypothesis that this may be one cause of t he neurologic complications of cystathionine beta-synthase deficiency. Betaine is effective in reducing cerebrospinal fluid homocysteine, bu t concentrations are still significantly raised during treatment.