Case 19,471: A Mystery Solved

The discovery of the link between homocysteine and heart disease owes much to an obscure case published in (he November 23, 1933, New England Journal of Medicine.  described an 8-year-old boy admitted to Massachu setts General Hospital after four days of headache, drowsiness, and vomiting. He died three days later. An autopsy revealed the cause of death: hardening of the arteries resulting in stroke. It was hardly a disease doctors expected to find in a child.

Thirty-two years later, a 9-year-old girl admitted to the same hospital had signs of homocystinuria, a genetic defect identified just a few years previously in which the liver can’t dispose of homocysteine, resulting in abnormally high levels of the amino acid. It turned out the little boy who had died in 1933 was her uncle.

The cases intrigued Kilmer S. McCully, M.D., then a pathologist at Massachusetts General Hospital. He began investigating the disease and found that in these children (and a 2-month-old baby) the arteries were thickened and damaged, even though there was no buildup of cholesterol.

In 1969 McCully published a paper outlining his discovery and proposing a link between B vitamins, methionine, and heart disease. (Homocysteine is converted into methionine, a harmless substance, with the help of B vitamins. When the body is deficient in B vitamins, the conversion is slowed and homocysteine levels rise.)

Although it took another 30 years before McCully’s theories became widely accepted, today doctors often screen high-risk patients for homocysteine levels.