NDiviDuAI with homocystinuria12 have been found to lack normal activity of the enzyme cystathionine synthetase. 3 In many of the patients progressive arterial disease develops in ildhood, frequently resulting in death from thrombosis in a vital organ45 In addition, con-genital dislocation of the lenses, mental retardation, and skeletal abnormalitieseg, osteoporosis, arachnodactyly, and pectus excavatum or pectus carinatum-usually are foundL5'Thevascular changes and other abnormalities encoumtered in homocystinuria have been attributed either to the metaboliceffects of the elevated tissueconcentrations of methionine, homocysteine, or homocystine, or to the metabolic con-sequences of decreased tissue concentrations of cystathionine found in the disease. 7

In a child dying with homocystinuria, cystathioninuria, and methyl malonic aciduria, secondary to an abnormality of cobalamin (B12) metabolism, arterial lesions have been discovered that resemble in a striking way many of those found in cystathionine synthetase deficiency. The vascular findigs i this patient will be presented and compared with those in a patient with cystathionine synthetase deficiency. Since the enzymatic abnormalities in both disorders share certain metabolic consequences, the conclusion has been reached that an elevated concentration of homocysteine, homocystine, or a derivative of hornocysteine is the common factor leading to arterial damage. The possible role of elevated concentrations of homocysteine or its deriva-tives in thepathogenesis of arteriosclerosis in individls free of known enzyme deficiencies will be discussed and interpreted with particular reference to the findings in experimentally produced arteriosclerosis.