Abstract: . . .  homocystinuria caused by deficiency of methylenetetrahydrofolate reductase, a folate- dependent enzyme, was also found by other investi- gators to have widespread arteriosclerotic plaques, independently corroborating this conclusion. Early reports of the pathological manifestations of homocystinuria attributed the vascular changes to a lathryogenic effect of homocysteine on the connective tissues of arteries because of a molecular resemblance of homocysteine to penicillamine, a well-known lathryo- genic compound. 4 Subsequent study of the role of homo- cysteine, however, has shown that moderate elevations of blood homocysteine levels are a potent independent risk factor for human arteriosclerotic vascular disease in the general population. 5 In classic cases of Marfan Syndrome the vascular mani- festations are principally dilation of aorta and aortic valve with cystic medial necrosis and predisposition to dissecting aneurysm of aortic arch. In homocystinuria the vascular manifestations are principally accelerated arteriosclerosis with predisposition to arterial and  . . .
. . .  results from these trials may suggest a similar approach to preventing morbidity and mortality in Marfan Syndrome, opening a further field of investigation. References 1. Mudd SH, Skovby F, Levy HL et al. The natural history of homo- cystinuria due to cystathionine beta synthase deficiency. Am J Hum Genet 1985; 37 :131. 2. Schimke RN, McKusick VA, Huang T et al. Homocystinuria. Studies of 20 families with 38 affected members. JAMA 1965; 193 :7119. 3. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis . Am J Pathol 1969; 56 :11128. 4. Gibson JB, Carson NAJ, Neill DW. Pathological findings in homocystinuria. J Clin Pathol 1964; 17 :42737. 5. McCully KS. Homocysteine and vascular disease. Nature Med 1996; 2 :3869. 6. McCully KS. Chemical pathology of homocysteine. I. Atherogenesis. II. Carcinogenesis and homocysteine thiolactone metabolism. III. Cellular function and aging. Ann Clin Lab Sci 1993; 23 :47793, 1994; 24: 2759, 134152. 1996 Editorial  . . .
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