Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease

N Engl J Med. 1985 Sep 19;313(12):709-15. doi: 10.1056/NEJM198509193131201.


Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency. It is unknown whether heterozygosity for homocystinuria predisposes to premature vascular disease. We explored the frequency of excessive homocysteine accumulation after standardized methionine loading in 75 patients presenting with clinical signs of ischemic disease before the age of 50:25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures. Because the frequency of heterozygosity for homocystinuria in the normal population is 1 in 70 at the most, we conclude that this condition predisposes to the development of premature occlusive arterial disease, causing intermittent claudication, renovascular hypertension, and ischemic cerebrovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arterial Occlusive Diseases / blood
  • Arterial Occlusive Diseases / etiology*
  • Arterial Occlusive Diseases / genetics
  • Cerebrovascular Disorders / blood
  • Cerebrovascular Disorders / etiology*
  • Cerebrovascular Disorders / genetics
  • Female
  • Heterozygote*
  • Homocysteine / blood
  • Homocystinuria / blood
  • Homocystinuria / complications
  • Homocystinuria / genetics*
  • Humans
  • Male
  • Menopause
  • Methionine
  • Middle Aged
  • Risk
  • Sex Factors


  • Homocysteine
  • Methionine