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

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Lipoprotein Lipase (LPL-) Deficiency, familial [E78.9]

OMIM numbers: 238600, 609708 (LPL)

Dr. med. Hanns-Georg Klein

Scientific Background

Primary LPL deficiency (hyperlipoproteinemia type I) is a rare autosomal recessive metabolic defect, characterized by severely increased serum triglyceride levels (up to 30,000 mg/dl) and chylomicronemia (milky white serum). LPL, an enzyme produced by the liver, plays a major role in the hydrolytic degradation of lipoproteins rich in triglyceride, chylomicrons in particular. The diagnosis is usually established in association with recurring pancreatitis (differential diagnosis: hereditary pancreatitis). Other frequent phenotypical manifestations include eruptive xanthomas and hepatomegaly. Dairy intolerance and unclear abdominal pain during childhood are characteristic for an anamnesis. Treatment of the pancreatic signs and symptoms involves a low fat diet and alcohol abstinence. The administration of fibrates, which increase the expression of LPL via the PPARα pathway, is problematic if no functioning allele is present (see also Apo C-II deficiency). Individuals with classic, primary LPL deficiency are at no higher risk of coronary heart disease.

Hyperlipoproteinemia type I is caused by homozygous or compound heterozygous mutations in the LPL gene on chromosome 8. In rare cases, LPL deficiency may be caused by mutations in the APOC2 gene, the most important co-factor of LPL. A temporary loss of function of APOC2 (e.g. in association with chemotherapy) has been described and may cause the clinical picture of hyperlipoproteinemia type I. However, in combination with other genetic factors, heterozygosity — also in variants in the regulatory elements of the LPL gene — seems to increase the risk of vascular disease (e.g. LPL-N291S). To determine the LPL activity in vitro, it is necessary to separate the enzyme from its heparan sulfate binding sites prior to taking a blood sample (post-heparin LPL activity). The EDTA plasma sample must be frozen in liquid nitrogen immediately. Recently, mutations in the APOA5 gene have been described in association with hypertriglyceridemic states, as well.