What Is the Most Common Genetic Disease in the United States?

The most common inherited fatal disease in the United States is an autosomal recessive condition called hemochromatosis. Approximately 1 of every 10 Americans is a carrier (heterozygous for a normal allele and a defective allele) and almost 1 in 250 is homozygous for the defective allele. This means that about 1.5 million people in the United States alone are at risk of dying from complications caused by this disease. For comparison, 1 of 25 is a carrier of the cystic fibrosis allele, and 1 in 2500 is a homozygote who actually develops cystic fibrosis.

Hemochromatosis is caused by the uptake of excessive amounts of iron by the intestines. Although we all need iron, particularly in the hemoglobin that carries oxygen in our red blood cells, too much iron is extremely toxic. The excess iron becomes deposited into tissues such as the liver, heart, and pancreas, eventually interfering with the functioning of these vital organs. So much iron accumulates that some individuals with hemochromatosis have reportedly set off the metal detectors in airport security checks! Damage caused by the excessive iron accumulation causes complications such as cirrhosis and cancer of the liver, heart disease, and diabetes, normally beginning in middle age. However, years before they are diagnosed, people with hemochromatosis may display widely varying symptoms, including chronic fatigue, abdominal pain, and a bronzed skin coloration.

A simple blood test for hemochromatosis measures the amount of iron in the serum as well as the amount of blood proteins that bind to iron (ferritin and transferrin). A liver biopsy then can confirm the diagnosis. The good news is that, if the tests reveal you do have this disease, the treatment is simple: frequent blood withdrawal. When blood is removed, iron is also removed, eventually lowering the overall iron amounts in the body. After hemochromatosis is diagnosed, the physician may prescribe removal of a unit (pint) of blood once or twice a week until the iron levels are reduced to normal ranges. To maintain these lower iron levels, an individual may then have blood withdrawn four to eight times each year. What happens to all that blood? Although there are arguments that support use of this blood for donation, current policy is to prevent people with hemochromatosis from donating blood. In fact, it COSTS them about $200 each time they give up their unit of blood, which is subsequently destroyed.

Mercator Genetics recently reported in the prestigious journal Nature that the company had identified the gene for hemochromatosis. This gene, called HLA-H, is on chromosome 6 and appears to encode a protein that is related to those that determine tissue compatibility (these are the proteins tested to see if a person is a compatible tissue donor). They found that many people with hemochromatosis have a mutation that changes amino acid 282 in the HLA-H protein from cysteine to tyrosine. How this defect causes increased uptake of iron is not understood at present, but commercial genetic tests are now available for the disease. It is hoped that knowing the gene responsible for hemochromatosis will also provide new avenues for treatment.

For related information, refer to your textbook Chapter 11, section 11) How Are Single-Gene Disorders Inherited?