THIAMINE (VITAMIN-B1) SUPPLEMENTATION DOES NOT REDUCES FASTING BLOOD HOMOCYSTEINE CONCENTRATION IN MOST HOMOZYGOTES FOR HOMOCYSTINURIA

Homozygotes for homocystinuria due to cystathionine synthase (CS) defi ciency accumulate homocysteine and methionine in their blood and tissu es. High-dose pyridoxin, folic acid, vitamin B12, or betaine are thera peutical options to lower the elevated homocysteine concentration. The se compounds stimulate the transsulfuration or remethylation of homocy steine. Despite such treatment, elevated blood homocysteine concentrat ions may persist in many homocystinurics. Therefore, it is warranted t o study alternative regimen to reduce the blood homocysteine concentra tion in homocystinurics. Apart from entering the transsulfuration path way, methionine can be catabolized via the transamination pathway, by conversion into 4-methylthio-2-oxobutyrate (MTOB), followed by oxidati ve decarboxylation of MTOB to 3-methylthiopropionate. Thiamine pyropho sphate, the active form of thiamine, is a cofactor of the supposed rat e-limiting oxidative decarboxylation in the transamination of methioni ne. The effect of thiamine administered in 2 or 3 daily doses of 25 mg orally, was studied in nine homozygote CS deficient patients. Methion ine levels decreased in 6 out of 9 patients. In 8 out of 9 patients, h owever, the levels of plasma homocysteine remained virtually unchanged , as did the serum transamination metabolites in all patients. We conc lude that vitamin B1 cannot be used as an additional homocysteine-lowe ring treatment in most homozygotes for homocystinuria.