Hyperlipoproteinemias

Hyperlipoproteinemias are disorders characterized by abnormal blood levels of lipoproteins, reflecting defects in lipoprotein metabolism. They may be inherited or acquired and are a subset of dyslipidemias. Patterns of elevation—triglycerides, cholesterol, or both—guide diagnosis and treatment.

Classification is based on the Fredrickson-Levy-Luyet system, grouping types I–V by the predominant lipoprotein abnormality. Type I: familial hyperchylomicronemia with high chylomicrons and triglycerides. Type IIa: familial hypercholesterolemia with high LDL. Type IIb: elevated LDL and VLDL. Type III: dysbetalipoproteinemia with IDL and remnants (ApoE2/E2). Type IV: hypertriglyceridemia with high VLDL. Type V: chylomicrons and VLDL elevated.

Causes and risks. Inherited forms stem from mutations in LPL, APOC2, LDLR, APOB, or APOE. Secondary factors include diabetes, hypothyroidism, nephrotic syndrome, obesity, alcohol use, and certain medications. The cardiovascular risk and pancreatitis risk depend on the type and severity.

Clinical features and diagnosis. Some patients are asymptomatic; others have xanthomas or corneal arcus. Severe hypertriglyceridemia can cause pancreatitis. Evaluation includes a fasting lipid panel, apolipoproteins, and, when indicated, lipoprotein analysis or genetic testing.

Management. Emphasis is on lifestyle modification and risk reduction. Treatments vary by type: statins for LDL; fibrates or omega-3 fatty acids for triglyceride-rich types; PCSK9 inhibitors for severe familial hypercholesterolemia. Type I focuses on dietary fat restriction; Type III may respond to fibrates and bile-acid sequestrants. Regular monitoring is advised.