Chylomicronemia syndrome

Signs and symptoms

The condition often presents in infancy with colicky pain and failure to thrive. In women, estrogen use or first pregnancy can trigger initial manifestation.

Recurrent abdominal pain and acute pancreatitis are the most common clinical features. Eruptive xanthomas occur in about half of patients, along with lipaemia retinalis and hepatosplenomegaly. Pancreatitis can become chronic, leading to pancreatic insufficiency and diabetes.

Diagnosis

Lab tests reveal massive chylomicron accumulation and severe hypertriglyceridemia, with fasting plasma appearing creamy. Familial LPL deficiency is suspected when secondary causes such as diabetes, alcohol, or certain medications are absent. Other gene mutations affecting triglyceride-rich lipoprotein catabolism (e.g., ApoC2, ApoA5, LMF-1, GPIHBP-1, GPD1) should also be considered.

Confirmation requires detection of homozygous or compound heterozygous pathogenic variants in LPL with low or absent enzyme activity. Lipid measurements show milky plasma and triglycerides above 2000 mg/dL. LPL activity and mass are reduced or absent in post-heparin plasma.

Treatment

Management aims to prevent pancreatitis attacks and reduce long-term cardiovascular risk. Olezarsen (Tryngolza) was approved in the United States in December 2024. Alipogene tiparvovec (Glybera), a gene therapy, received European Commission approval in 2012 for adults with confirmed familial LPLD and severe pancreatitis despite dietary fat restriction. It was the first gene therapy authorized in the European Union, priced at about $1 million per treatment.