Treatment of hyperhomocyst(e)inemia: physiological basis

Hyperhomocyst(e)inemia (HCY) is caused either by genetic or nongenetic defect(s), and the clinical severity of HCY is correlated with the biochemical abnormality. Treatment of HCY is approached on the basis of its etiology and severity of defect. The preferred method of treatment for genetic HCY is activation of mutant enzyme activity with the cofactor or the precursor of cofactor. If HCY does not respond to this treatment, pharmacological doses of betaine or folic acid should be used to enhance the alternative pathway of homocysteine turnover. Phenotypic expression of minor genetic defects, such as heterozygous cystathionine synthase deficiency and thermolabile methylenetetrahydrofolate reductase (MTHFR) can be amplified or masked by nongenetic (nutritional) factor(s). Hence, supplementation of folic acid, vitamin B-12, pyridoxine and choline to maintain their serum concentrations above low normal range may satisfactorily prevent the development of moderate HCY due to a minor genetic defect.