Scientific background:

Summary: The protein product, an intravascular enzyme, degrades very low density lipoproteins and chylomicrons. A deficiency in this enzyme activity results in chylomicronaemia or hypertriglyceridaemia.

Gene: The size of LPL gene is about 30kb. This gene is located on chromosome 8 (8p22). The gene has 10 exons.

Pathology: The l Lipoproteinlipase is a glycosylated enzyme. It is produced by adipocytes and secreted into blood stream. Its function is lipolytic degradation of triglycerides in triglyceride rich lipoproteins. The important cofactor on these lipoproteins is Apolipoprotein C2.

Clinical signs: The clinical signs of lipoprotein lipase deficiency and apolipoprotein C2 defects are identical. Biochemically a hyperlipoproteinemia type I can be considered in homozygous state. In heterozygous state there is rather a mixed hyperlipidemia evident. That can be type V according to classification of Fredrickson. There is often recurrent pancreatitis seen in these patients. The skin may show xanthomas.

Epidemiology: The frequency of homozygous LPL deficiencies is 1:1,000,000.

Interpretation: This test is appropriate to confirm lipoprotein lipase deficiency. This is much more easily to perform than direct measurement in plasma. In combination with apolipoprotein C2 testing it is even a much more reliable test for insufficient lipoprotein degradation. The patients have to be treated with a strong regiment of fat free diet.

Test strategy: Patients with excessive triglyceridemia and/or recurrent pancreatitis.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		medium
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Multiplex Ligation-Dependent Probe Amplification
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Brunzell JD in Scriver CR et al. (eds): The Metabolic and Molecular Bases of Inherited Disease, 7th ed. Chapter 59 (1997)
Benlian P et al. (1996) Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene.
Knopp RH et al. (1999) Drug treatment of lipid disorders.