Hyperlipoproteinemia type 1

Hyperlipoproteinemia type 1, also known as familial lipoprotein lipase (LPL) deficiency, familial hyperchylomicronemia, or familial chylomicronemia syndrome (FCS), is a rare inherited disorder of lipid metabolism characterized by a severe elevation of triglycerides and chylomicrons in the blood. The condition is caused by a deficiency or dysfunction of the enzyme lipoprotein lipase, which is essential for breaking down triglyceride-rich lipoproteins. In some cases, the disorder results from a deficiency of apolipoprotein C-II, a cofactor required for LPL activity. Mutations in the LPL gene (and less commonly APOC2, APOA5, LMF1, or GPIHBP1 genes) are responsible for this condition. The hallmark clinical features include recurrent episodes of acute pancreatitis, which can be life-threatening, eruptive xanthomas (small yellowish skin lesions typically appearing on the trunk, buttocks, and extensor surfaces of the limbs), hepatosplenomegaly (enlargement of the liver and spleen due to lipid accumulation), and lipemia retinalis (a milky appearance of retinal blood vessels). Patients often present in childhood with abdominal pain, and their blood plasma may appear milky or creamy (lactescent) due to the extreme elevation of chylomicrons. Triglyceride levels typically exceed 1,000 mg/dL and can reach over 10,000 mg/dL. The primary treatment for hyperlipoproteinemia type 1 is a very strict low-fat diet, typically restricting dietary fat to 15–20 grams per day or less than 15% of total caloric intake. Medium-chain triglycerides (MCTs) may be used as a dietary supplement since they are absorbed directly into the portal circulation without requiring chylomicron formation. Unlike other forms of hyperlipidemia, this condition does not respond well to standard lipid-lowering medications such as statins or fibrates. Gene therapy (alipogene tiparvovec, marketed as Glybera) was previously approved in Europe but has since been withdrawn from the market. Volanesorsen, an antisense oligonucleotide targeting apolipoprotein C-III, has been approved in some regions for the management of familial chylomicronemia syndrome. Avoidance of alcohol and other secondary causes of hypertriglyceridemia is also recommended.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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