SCIENTIFIC BACKGROUND

LPL

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.

 

References
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

GENES

LPL

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Have you ever wondered how jet-setting across the globe might affect your gut health? A recent study has dug into this intriguing question, revealing...

Read more

In June 2023, Medicover Genetics attended the 56th conference of the European Society of Human Genetics (ESHG) which took place in Glasgow, Scotland....

Read more

Vitamin D, also known as “the sunshine vitamin”, is a fat-soluble vitamin that helps the body absorb calcium and phosphate, which are essential f...

Read more

Every movement our body makes is controlled by a long, thin, tube-like structure called the “spinal cord”. The spinal cord is part of our nervous...

Read more

Genetic variant databases are vital for interpreting genetic variations in clinical settings and research. However, misclassified variants can create...

Read more

A recent article published by our team in the International Journal of Molecular Sciences [1], aimed to evaluate the prevalence, prognostic and predi...

Read more

A healthy, nutritious and well-balanced diet is always important for a person’s well-being, and it is even more so during pregnancy as the developi...

Read more

The sun is hot and you are sweating. Most of us know how it feels to sweat, and when we sweat. This is a normal bodily response to an increase in tem...

Read more

All about the pancreas The pancreas is a pear-shaped organ that is located at the upper left side of the abdomen, behind the stomach. It has two m...

Read more

The father of genetics is Gregor Mendel. Mendel was an Austrian monk, whose experiments breeding pea plants in the monastery garden led to breakthrou...

Read more