Hyperchylomicronemia

Hyperchylomicronemia is a disorder characterized by marked elevation of chylomicrons in fasting plasma, typically with severe hypertriglyceridemia. It most commonly refers to familial chylomicronemia syndrome (FCS), an autosomal recessive condition caused by defective lipoprotein lipase activity or its cofactors, though secondary forms occur with obesity, diabetes, alcohol use, estrogens, or certain drugs.

Pathophysiology: In primary forms, mutations in LPL, APOC2, APOA5, LMF1, or GPIHBP1 impair hydrolysis of triglyceride-rich lipoproteins, allowing accumulation of chylomicrons after fat intake. This produces lipemic (cloudy) fasting plasma.

Clinical features: TG levels often exceed 1000 mg/dL. Patients may develop eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, abdominal pain, and recurrent pancreatitis. Secondary triggers can exacerbate manifestations.

Diagnosis: Diagnosis relies on a fasting lipid panel showing extreme hypertriglyceridemia and the presence of chylomicrons. Exclusion of secondary causes is important. Genetic testing can identify causative mutations.

Management: The cornerstone is strict dietary fat restriction (very low-fat diet) and avoidance of fasting. Pharmacologic therapies such as fibrates or omega-3 fatty acids have limited efficacy in classic LPL deficiency; treatment must be individualized. In acute pancreatitis, plasmapheresis can rapidly reduce triglycerides. Gene therapy approaches have been explored, notably LPL-based therapies, but are not widely available.

Prognosis: Recurrent pancreatitis is a major complication; outcome depends on triglyceride control and underlying genotype.