Dysbetalipoproteinemia

Dysbetalipoproteinemia, also known as type III hyperlipoproteinemia or broad beta disease, is a hereditary disorder of lipoprotein metabolism. It results from the apolipoprotein E2/E2 genotype, which causes defective clearance of chylomicron and very low-density lipoprotein (VLDL) remnants. Consequently, there is accumulation of beta-VLDL remnants in the plasma, leading to elevations in both total cholesterol and triglycerides.

The condition is inherited in an autosomal manner with incomplete penetrance. The E2 variant of apolipoprotein E has reduced receptor affinity, and individuals with E2/E2 usually require secondary factors such as obesity, diabetes, hypothyroidism, estrogen therapy, or other metabolic stresses to manifest clinically. The lipid abnormality is predominantly a remnant lipoprotein disorder, often with elevated remnant cholesterol.

Clinical features include cutaneous signs such as tuberous xanthomas and distinctive palmar xanthomas. Patients may develop premature atherosclerotic cardiovascular disease, including coronary artery disease or peripheral vascular disease; symptoms can be subtle until adulthood.

Diagnosis is based on a typical fasting lipid profile showing elevations of both cholesterol and triglycerides, with a pattern consistent with remnant lipoproteins. ApoE genotyping reveals E2/E2. Electrophoretic or newer lipoprotein analyses may show beta-VLDL remnants. Low HDL levels may be present.

Management focuses on reducing remnant lipoproteins and controlling secondary factors. Lifestyle modification is important, including weight management, smoking cessation, and treatment of diabetes or thyroid disease if present. Lipid-lowering therapy typically starts with statins; fibrates or niacin can be added to better reduce triglyceride-rich remnants. Omega-3 fatty acids and ezetimibe may be used, and PCSK9 inhibitors can be considered as adjuncts. Regular monitoring and cardiovascular risk assessment are recommended due to the increased atherosclerotic risk.