What is FH?

Mutations in LDL receptor gene. Courtesy of Dr. Joseph Goldstein, University of Texas Southwestern Medical School at Dallas.

Who is at risk?

About one person in 500 carries one FH allele and has an increased risk of heart disease. That means that nearly 500,000 Americans are have one defective allele. Most don't know it. About one person in a million has two FH alleles; these people often have heart attacks and die before age 20. Xanthomas (lumps of fatty tissue) are often a sign of this serious form of FH. People descended from French Canadians, South African whites, Finns, and Christian Lebanese often have the two FH alleles. In 1973, Drs. Michael Brown and Joseph Goldstein and their colleagues at the University of Texas Southwestern Medical School at Dallas discovered the LDL receptors in the liver. Then they proved that a lack of LDL receptors causes a buildup of cholesterol. By purifying the LDL receptor protein, they isolated the gene responsible for FH in 1984. They received a Nobel Prize for describing how the gene, the protein, the receptors, and LDL work in the body's cholesterol system.

Patient with xanothomas. Courtesy of Dr. Joseph Goldstein, University of Texas Southwestern at Dallas.

Dr. Michael Brown and Dr. Joseph Goldstein and the Nobel Prize. Courtesy of Dr. Joseph Goldstein, University of Texas Southwestern Medical School at Dallas.

How is FH treated?

People who have only one FH allele can follow a low-fat, low-cholesterol diet, exercise, and take special drugs to reduce their risk of heart disease. People with two FH alleles may benefit from "apheresis" every two weeks, a process that removes LDL from their blood. In the first FH gene therapy trial, researchers removed 10% of a woman's liver and grew cells from her liver in the laboratory. Then they altered a virus in the laboratory so that it contained the missing gene but could not reproduce itself.  They added the virus to the liver cells, and the virus inserted the missing gene into the cells.  Finally, the reinjected the "repaired" cells into her.  Her cholesterol level lowered moderately, but whether the therapy worked or the level decreased for some other reason is unclear. Five patients have been treated with mixed results.
		Low fat food and excercise. Courtesy of National Cancer Institute.

	FH is a dominant trait. Mutation sin LDL receptor gene

Slide of Dr. Wilson's experiments. Courtesy of the National Human Genome Research Institute.