Chylomicronemia

Signs and symptoms

The disease often presents in infancy with colicky pain, failure to thrive, and other features of chylomicronemia syndrome. In women, estrogen use or first pregnancy can trigger initial manifestation.

Recurrent abdominal pain and acute pancreatitis are the most common clinical manifestations at all ages. Eruptive xanthomas occur in about half of patients, along with lipaemia retinalis and hepatosplenomegaly. Acute pancreatitis can be life-threatening and may lead to chronic pancreatic insufficiency and diabetes.

Diagnosis

Lab tests reveal massive chylomicron accumulation and severe hypertriglyceridemia; fasting plasma appears creamy (lactescent). Familial LPL deficiency is considered in anyone with severe hypertriglyceridemia and chylomicronemia syndrome after excluding secondary causes such as diabetes, alcohol, or certain medications. Other loss-of-function mutations in genes like ApoC2, ApoA5, LMF-1, GPIHBP-1, or GPD1 should also be considered. Diagnosis is confirmed by detecting homozygous or compound heterozygous pathogenic variants in LPL with low or absent lipoprotein lipase enzyme activity.

Lipid measurements show milky, lipemic plasma and severely elevated fasting triglycerides above 2000 mg/dL. LPL enzyme activity and mass are low or absent in post-heparin plasma. Molecular genetic testing identifies mutations in the LPL gene on chromosome 8p22.

Treatment

Treatment aims to prevent pancreatitis attacks immediately and reduce long-term cardiovascular disease risk. Olezarsen (Tryngolza) was approved for medical use in the United States in December 2024. In 2012, the European Commission approved alipogene tiparvovec (Glybera), a gene therapy for adults with confirmed familial LPLD who have severe or multiple pancreatitis attacks despite dietary fat restrictions. Glybera was the first gene therapy authorized in the European Union, priced at about $1 million per treatment; as of 2016, only one person had been treated commercially, and a total of 31 people received it, mostly in clinical trials before it was withdrawn.