SCIENTIFIC BACKGROUND
Due to its central role in the activation of lipoprotein lipase (Lpl), apolipoprotein C-II (Apo C-II) plays an important role in the metabolism of triglyceride-rich lipoproteins, especially chylomicrons. Primary Apo C-II deficiency is a rare autosomal recessive inherited metabolic defect characterized by extremely elevated serum concentrations of triglycerides (up to 30,000 mg/dl) and chylomicrons (milky creamy serum, Fredrickson's hyperlipidemia type I). In addition to the hereditary form, an acquired, reversible form of apo C-II deficiency has also been described which can be caused, for example, by chemotherapy. The diagnosis is mostly made in the context of recurrent pancreatitis (DD: hereditary pancreatitis); eruptive xanthomas and hepatomegaly are common phenotypic features that occur only in the congenital form. Apo C-II deficiency is not associated with increased coronary risk. Treatment consists of a low-fat diet, alcohol abstinence, and administration of fibrates when appropriate. Fibrates induce the expression of Lpl through activation of the transcription factor PPARalpha, which can further lower serum triglyceride concentrations. Therefore, fibrate therapy is only beneficial if the LPL gene is intact. Because LPL deficiency is also associated with type I hyperlipidemia, molecular genetic analysis of the LPL gene may be useful in the context of treatment planning.
The disease is caused by homozygous or mixed heterozygous pathogenic variants in the APOC2 gene that secondarily lead to functional Lpl deficiency. The APOC2 gene is located on chromosome 19 and is localized in the APOE/APOC1/APOC2 gene cluster.
References
Wolska et al. 2017, Atherosclerosis 267:49 / Mendoza-Barberá et al. 2013, J Lipid Res 54:649 / Brahm et Hegele 2013, Nutrients 5:981 / Burnett et al. 2017, GeneReviews® [Internet]