NDDIC News

Gene Test for Hemochromatosis Could Save Lives With Wider, Earlier Use

In 1998, a team of medical researchers at the Saint Louis University School of Medicine provided valuable insight into the genetic mechanisms that contribute to hereditary hemochromatosis (HH), a common autosomal recessive disorder that results in increased iron absorption. (An autosomal recessive disorder occurs when the defective gene is passed on by both parents.) This knowledge helped lead to the development of a genetic test for screening that allows physicians to detect the disease early enough to prevent the deadly consequences of untreated HH. According to recent research, however, many physicians may not use or know about this screening tool.

HH can progress silently until toxic iron deposits in the liver and other organs cause cirrhosis, liver cancer, diabetes, heart failure, and, in some cases, death. With early detection, the simple act of regular blood-letting (called prophylactic phlebotomy) can prevent iron buildup.

The Missouri research team was supported in part by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The team was testing the theory that a mutation in a gene identified as HFE was responsible for HH.

To test the gene, researchers created a mouse model for the human disease. They identified the murine homologue, or mouse version, of the HFE gene and disrupted it in a number of mice. The gene-knockout mice (those with the disrupted gene) showed iron concentrations in the liver that were eight times higher than those of their normal littermates.

Before this study, scientists knew that 90 percent of patients with HH had the same mutation (C282Y) in the HFE gene. But they could not be sure whether the mutation was responsible for the defect in iron metabolism or whether it was just an innocent abnormality linked to an as-yet-unidentified gene that actually caused the problem. The mouse knockout model has helped confirm that the HFE mutation is the cause of HH and paved the way for the commercial development of a genetic test.

The new HFE mutation analysis test has not replaced the need for traditional diagnostic procedures, which include measuring the amounts of iron in the blood and the body, and liver biopsies are still needed to check for iron deposits and cirrhosis. But the DNA-based test is useful in screening family members of people with HH for the potential to develop the disease.

Unfortunately, indications are that the test is not being widely used for this purpose. As reported in the May 2000 issue of the Southern Medical Journal, a team of researchers recently surveyed physicians in Arkansas to determine how widely knowledge and use of the test had spread. Results indicated that only 21 percent of the physicians surveyed knew of the test, and only 10 percent knew it was available in Arkansas. Further, only 3 percent of those responding had actually given the test, and only one physician had used the test to screen the relatives of a patient with confirmed HH.

NIH Publication No. 01–4552
March 2001