Homocystinuria, arteriosclerosis, methylmalonic aciduria, and methyltransferase deficiency: a key case revisited.

The original case of Cb1 C disease with homocystinuria, cystathioninuria, methylmalonic aciduria, and hypomethioninemia was reexamined because of its importance in the discovery of the homocysteine theory of arteriosclerosis. The vascular lesions in the case consist of proliferative fibrous intimal plaques and focal necrosis of the artery wall, which are attributed to effects of excess homocysteine thiolactone on aggregation of low-density lipoproteins (LDL) and on respiration of endothelial cells. Atrophic, metaplastic, and dysplastic changes within the gastric mucosa are attributed to effects of excess homocysteine thiolactone on synthesis of keratin, sulfomucins, and nucleoproteins within affected cells. The case illustrates how investigation of an inborn error of metabolism illuminates pathophysiological disease processes, normal metabolic pathways, and important aspects of cellular function.