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

You are here: Molecular Genetics » Apolipoprotein C-II Deficiency

Apolipoprotein C-II Deficiency (Hyperlipoproteinemia Type I) [78.6]

OMIM numbers: 207750, 608083 (APOC2), 238600, 609708 (LPL), 606368 (APOA5)

Dr. med. Hanns-Georg Klein

Scientific Background

Apolipoprotein C-II (Apo C-II) is centrally involved in the activation of lipoprotein lipase (LPL) and thus plays an important role in the metabolism of triglyceride-rich lipoproteins, especially chylomicrons. Primary Apo C-II deficiency is a rare, autosomal recessively inherited metabolic defect (Fredrickson type I hyperlipoproteinemia) characterized by extremely elevated serum concentrations of triglycerides (up to 30,000 mg/dl) and chylomicrons (lactescent (milky) serum). Besides the hereditary type an acquired reversible form of Apo C-II deficiency exists, that may be caused for instance by a chemotherapy. The diagnosis is usually made in context with recurrent pancreatitis (DD: hereditary pancreatitis) where eruptive xanthomas and hepatomegaly are some common phenotypic manifestations; however, they only appear with the inherited type. Apo C-II deficiency is not associated with an increased coronary risk. Treatment consists of low-fat diet, abstinence from alcohol and optionally the administration of fibrates. Fibrates induce the expression of Lpl by activation of the transcription factor PPAR-α which leads to a further decrease of triglycerid concentration in the serum. Thus, a fibrate therapy is only effective with an intact LPL gene. As LPL deficiency is associated with type I hyperlipidemia as well, an analysis of the LPL gene may be advisable when planning therapy.

The disease is caused by homozygous or compound heterozygous mutations in the APOC2 gene which secondarily lead to a functional LPL deficiency. The APOC2 gene is found on chromosome 19 and is located close to the APOE/APOC1/APOC2 gene cluster. Recently, in some families with hyperlipoproteinemia type I but with no mutations in the APOC2 and LPL gene, mutations in the APOA5 gene were identified. Apolipoprotein A-V seems to play a decisive role in the regulation of triglyceride metabolism, since already the heterozygous state leads to a disposition for hypertriglyceridemic conditions. The APOA5 gene is located close to the APOA1/APOC3/APOA4 gene cluster of which the gene products are involved in the homeostasis of the triglyceride metabolism.