Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Apolipoprotein B Deficiency (FLDB) [E78.6]

OMIM numbers: 144010, 107730 (APOB)

Dr. med. Hanns-Georg Klein

Scientific Background

Besides familial hypercholesterolemia (FH) which is predominantly caused by mutations in the LDL receptor gene, an additional autosomal dominant familial form occurs which is caused by mutations in the APOB gene (prevalence about 1:700–1,000). The gene product apolipoprotein B is a component of the LDL particle and serves as an ligand in receptor-mediated uptake of LDL into the cell. This impairment of LDL metabolism referred to as familial apolipoprotein B deficiency (Familial Ligand Defective Apo B, FLDB) is associated with a lower level of hypercholesterolemia compared to FH. Nevertheless, patients exhibit a significant coronary risk.

Prevalence of the most frequent mutations in the APOB gene, APOB-R3500Q and APOB-R3531C, is described as 1:450 and 1:3,000 in the general population which is about equivalent to the frequency of heterozygous LDL receptor defects. Already in the heterozygous state total cholesterol shows increased values by 70–95 mg/dl (APOB-R3500Q) and 45–65 mg/dl (APOB-R3531C) compared to controls due to the decreased affinity of ApoB to the LDL receptor. The APOB mutations R3500Q and R3531C can be found in 7% of all patients with a familial hypercholesterolemia. Homozygosity for FLDB is extremely rare, the phenotype resembles that of heterozygous FH.