In 1962, 30 years after the discovery by du Vigneaud have pathologic consequences. One potentially sig- of a new sulfur amino acid, homocysteine; Carson and nificant health outcome of such mild to moderate Neil reported two siblings with mental retardation in hyperhomocysteinemia is an increased risk of occlu- northern Ireland with elevated urinary homocystine. sive vascular disease. Homocysteine concentrations in Nearly simultaneously, Gerritsen and Waisman patients with vascular disease were, on average, 31 % greater than in normal controls. Prospective assess- identified increased homocystine in the urine of a mentally retarded infant in Wisconsin. Within two ment of vascular disease risk among men with higher years, Harvey Mudd, James Finkelstein, and their homocysteine concentrations indicated that plasma coworkers at the National Institutes of health (USA) homocysteine at only 12% above the upper limit of that the enzyme cystathionine ~- normal levels was associated with a 3. 4-fold increase had reported synthase was lacking in a liver biopsy specimen from in risk of acute myocardial infarction. Studies from another patient with homocystinuria. This was the original Framingham Heart Study cohort (USA) the first indication of a vitamin relationship to have shown strong, positive correlation between homocystinuria, because that enzyme has as its co- plasma homocysteine concentration and degree of factor vitamin B6 (pyridoxal phosphate). Thereafter, carotid stenosis.