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

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Hypobetalipoproteinemia, familial (FHBL) [E78.6]

OMIM numbers: 605019, 107730 (APOB)

Dr. med. Hanns-Georg Klein

Scientific Background

Familial hypobetalipoproteinemia is a heterogenous group of autosomal dominant disorders of the metabolism of apolipoprotein B-containing lipoproteins caused by a dysfunction of variants of apo B. As a crucial component of LDL and VLDL, Apo B plays a major part in both the hepatic synthesis (assembly) of VLDL and as ligand for the APO B/E or LDL receptor for the reabsorption of LDL through the liver. Due to the different properties of the mutated, in most cases shortened apo B polypeptides, the clinical phenotype varies and may in rare cases (null allele variants of the APOB gene) resemble abetalipoproteinemia.

The disease is caused by mutations in the APOB gene, which usually lead to expression of a truncated apo B protein. The hepatic secretion rate of apo B-containing lipoproteins correlates with the length of the shortened polypeptides. Aside from a moderate reduction of serum cholesterol or triglyceride concentration and weak deep tendon reflexes, heterozygous carriers (frequency approx. 1 in 3,000) hardly display any abnormalities. Treatment is required only if significant neurological disorders arise. In these cases, treatment consists of dietary measures as well as substitution of vitamin A and E, just as in the case of abetalipoproteinemia. Compared to the general population, heterozygous carriers are at a lower risk of coronary heart disease due to reduced LDL and VLDL levels.