Primary LPL deficiency is a rare, autosomal recessive metabolic defect that usually manifests in childhood and is characterized by extremely elevated serum concentrations of triglycerides (up to 30,000 mg/dl) and chylomicronemia (milky creamy serum) (Fredrickson's hyperlipidemia Type I). LPL, an enzyme produced by the liver, plays an important role in the hydrolytic degradation of triglyceride-rich lipoproteins, especially chylomicrons. The diagnosis is usually made in the context of recurrent pancreatitis (DD: hereditary pancreatitis); eruptive xanthomas and hepatomegaly are other common phenotypic manifestations. Characteristic history includes intolerance of dairy products and unexplained abdominal pain in childhood. Therapy for pancreatitic symptoms consists of low-fat diet (<20 g/day) and alcohol abstinence. Administration of fibrates, which increase expression of LPL via the PPAR-alpha pathway, is problematic in cases where no functional allele is available (see also Apo C-II deficiency). Individuals with classic, primary LPL deficiency do not have an increased coronary risk.
Type I hyperlipidemia is caused by homozygous or mixed heterozygous pathogenic variants in the LPL gene. Less commonly, LPL deficiency may be caused by causative variants in the APOC2 gene, the major cofactor for LPL. Passive loss of function of APOC2 (e.g., due to chemotherapy) has also been described and may lead to the clinical presentation of type I hyperlipidemia. However, heterozygosity, including for variants in the regulatory elements of the LPL gene, in combination with other genetic factors appears to promote increased vascular risk.
Determination of LPL activity in vitro requires dissolution of the enzyme from its heparan-sulfate binding sites before blood collection (post-heparin LPL activity). Immediate freezing of the EDTA plasma sample in liquid nitrogen must be ensured.
Caddeo at el. 2018, Nutr Metab Cardiovasc Dis. 28:158 / Burnett et al. 2017, GeneReviews® [Internet] / Rodrigues et al. 2016, J Clin Lipidol. 10:394 / Mendoza-Barberá et al. 2013, J Lipid Res 54:649 / Brahm et Hegele 2013, Nutrients 5:981 / Kei et al. 2012, Metabolism 61:906 / Brunzell et Dee in Scriver et al. 2001 (eds): The Metabolic and Molecular Bases of Inherited Disease, 8th Ed, Chapter 117