Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis.

TLDR: 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 hornocysteines is the common factor leading to arterial damage.

Abstract: NDiviDuAI with homocystinuria 12 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, congenital dislocation of the lenses, mental retardation, and skeletal abnormalitieseg, osteoporosis, arachnodactyly, and pectus excavatum or pectus carinatum-usually are foundL5' The vascular changes and other abnormalities encoumtered in homocystinuria have been attributed either to the metabolic effects of the elevated tissue concentrations of methionine, homocysteine, or homocystine, or to the metabolic consequences 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 derivatives in the pathogenesis of arteriosclerosis in individls free of known enzyme deficiencies will be discussed and interpreted with particular reference to the findings in experimentally produced arteriosclerosis.