Lipoprotein lipase deficiency
Lipoprotein lipase deficiency is a genetic disorder in which a person has a defective gene for lipoprotein lipase, which leads to very high triglycerides, which in turn causes stomach pain and deposits of fat under the skin, and which can lead to problems with the pancreas and liver, which in turn can lead to diabetes. The disorder only occurs if a child acquires the defective gene from both parents. It is managed by restricting fat in diet to less than 20 g/day.
Signs and symptoms
The disease often presents in infancy with colicky pain, failure to thrive, and other symptoms and signs of the chylomicronemia syndrome. In women the use of estrogens or first pregnancy are also well known trigger factors for initial manifestation of LPLD. At all ages, the most common clinical manifestation is recurrent abdominal pain and acute pancreatitis. The pain may be epigastric, with radiation to the back, or it may be diffuse, with the appearance of an emergent acute abdomen. Other typical symptoms are eruptive xanthomas, lipaemia retinalis and hepatosplenomegaly.Complications
Patients with LPLD are at high risk of acute pancreatitis, which can be life-threatening, and can lead to chronic pancreatic insufficiency and diabetes.Diagnosis
Lab tests show massive accumulation of chylomicrons in the plasma and corresponding severe hypertriglyceridemia. Typically, the plasma in a fasting blood sample appears creamy.Familial LPL deficiency should be considered in anyone with severe hypertriglyceridemia and the chylomicronemia syndrome. The absence of secondary causes of severe hypertriglyceridemia increases the possibility of LPL deficiency. In this instance besides LPL also other loss-of-function mutations in genes that regulate catabolism of triglyceride-rich lipoproteins should also be considered
The diagnosis of familial lipoprotein lipase deficiency is finally confirmed by detection of either homozygous or compound heterozygous pathogenic gene variants in LPL with either low or absent lipoprotein lipase enzyme activity.
Lipid measurements
· Milky, lipemic plasma revealing severe hyperchylomicronemia;
· Severely elevated fasting plasma triglycerides ;
LPL enzyme
· Low or absent LPL activity in post-heparin plasma;
· LPL mass level reduced or absent in post-heparin plasma;
Molecular genetic testing
The LPL gene is located on the short arm of chromosome 8 at position 22. More than 220 mutations in the LPL gene have been found to cause familial lipoprotein lipase deficiency so far.
Treatment
Treatment of LPLD has two different objectives: immediate prevention of pancreatitis attacks and long-term reduction of cardiovascular disease risk.Olezarsen was approved for medical use in the United States in December 2024.