Definitive diagnosis can be made only with gene or receptor analysis.

It is the primary determinant of hepatic LDL uptake, which normally processes approximately 70% of circulating LDL.

Two ligands on LDL bind to the receptor, apolipoprotein B-100 (apo B-100) and apo E.

LDL receptor analysis can be used to identify the specific LDL receptor defect, and LDL receptor or apo B-100 studies can help distinguish heterozygous FH from the similar syndrome of familial defective apo B-100.

Investigative therapies for homozygous and heterozygous FH include probucol, which causes regression of cutaneous and tendon xanthomas in patients with both homozygous and heterozygous FH but no long-term benefits for reduced coronary atherosclerosis, and gene therapy.

Untreated men are likely to develop symptoms by the fourth decade of life.

The onset of symptoms in women lags behind men by approximately 10-15 years.

Children are at risk for early coronary events, and sudden death or acute myocardial infarction may occur in patients as young as 1-2 years.

Without heroic interventions to lower blood cholesterol levels, survival beyond young adulthood is unlikely.

The LDL receptor binds apo E with higher affinity than apo B-100, and some mutations in the receptor may spare uptake of LDL by allowing binding to apo E.