Chylomicronemia Syndrome (Hyperlipoproteinemia Type 1) [E78.3]
Dr. med. Hanns-Georg Klein
Familial chylomicronemia syndrome (hyperlipoproteinemia type 1) is a rare, autosomal recessive inherited disorder of the chylomicron metabolism characterized by extremely high serum concentrations of triglycerides (up to 30,000 mg/dl) and a lactescent (milky) serum. The diagnosis is usually made in context with recurrent pancreatitis (DD: hereditary pancreatitis). Eruptive xanthomas and hepatomegaly are common phenotypical manifestations. Milk intolerance in childhood is often reported. The therapy of the pancreatic symptoms includes a low-fat diet, abstinence from alcohol and, in severe cases, a lipid apheresis.
The hepatic enzyme lipoprotein lipase (Lpl) which is located on the endothelial cells of extrahepatic capillaries plays a decisive role in the hydrolytic degradation of triglyceride-containing lipoproteins, especially chylomicrons. Homozygous or compound heterozygous mutations in the LPL gene lead to hyperlipoproteinemia type 1. A LPL deficiency can also be caused secondarily by mutations in the APOC2 gene, the most important cofactor for LPL. Moreover, mutations in the GPIHBP1 gene are described which lead to a defect of the transporter (glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1, GPIHBP1) of the lipoprotein lipase. Prior to a therapy of hypertriglyceridemia with fibrates which acts via transcriptional activation of LPL gene expression, it is advisable to check if a functional LPL allele is present. The determination of LPL activity in vitro requires the release of the enzyme from its heparin sulphate binding sites before blood sampling (post heparin LPL activity). The correct sampling procedures must be followed as well as ensuring the immediate freezing of the EDTA plasma sample in liquid nitrogen or dry ice.