From the Guidelines
Familial type 3 hyperlipoproteinemia, also known as dysbetalipoproteinemia, is a genetic disorder characterized by elevated levels of cholesterol and triglycerides in the blood due to a defect in apolipoprotein E (apoE), which impairs the clearance of chylomicron and VLDL remnants from the bloodstream 1. This condition typically manifests in adulthood, often after age 20, and is more common in men than women. Patients may develop xanthomas (yellowish cholesterol deposits) on the skin, particularly on the palms, and are at increased risk for premature atherosclerosis and coronary artery disease. Some key features of this condition include:
- Elevated total cholesterol and triglycerides with a characteristic ratio
- Impaired receptor-mediated clearance of chylomicron and VLDL remnants
- Increased risk of cardiovascular and peripheral vascular disease
- Often requires additional factors such as obesity, diabetes, or hypothyroidism for expression
- Diagnosis involves lipid profile testing and genetic testing for apoE variants
- Treatment focuses on lifestyle modifications and medications such as statins and fibrates to lower lipid levels 1. It's worth noting that the expression of the lipid phenotypes makes identification difficult, and the combination of both family screening and upper 10th percentile apo B levels is often needed for diagnostic confirmation 1. The condition follows an autosomal recessive inheritance pattern, requiring two defective apoE genes, and is more likely to manifest when combined with other factors like obesity, diabetes, or hypothyroidism 1.
From the Research
Definition and Characteristics
- Familial type 3 hyperlipoproteinemia, also known as Familial Dysbetalipoproteinemia, is a genetic disorder characterized by increased plasma triglyceride and remnant lipoproteins, such as chylomicron remnants and VLDL remnants (IDL) 2.
- This condition is typically associated with homozygosity for the apolipoprotein E2 isoform, but can also be caused by dominant rare missense variants in the APOE gene 3.
- Patients with Familial Dysbetalipoproteinemia present with roughly equimolar elevations of cholesterol and triglyceride due to the accumulation of remnant lipoprotein particles 3.
Clinical Features
- Clinical features of Familial Dysbetalipoproteinemia include tuberoeruptive xanthomas, palmar xanthomas, and premature vascular disease 3.
- Patients often have high levels of plasma triglyceride and total cholesterol, with mean levels ranging from 374 to 426 mg/dL and 256 to 719 mg/dL, respectively 2, 4.
- There is a high prevalence of obesity, xanthomas, and atherosclerosis, especially peripheral vascular disease, in patients with this condition 2, 4.
Diagnosis
- Diagnosis of Familial Dysbetalipoproteinemia is based on the presence of increased remnant lipoproteins, such as IDL, and can be confirmed by genetic analysis of the APOE gene 5, 3.
- A diagnostic algorithm involving total cholesterol, triglycerides, and apolipoprotein B (apoB) can be used to distinguish Type III hyperlipoproteinemia from mixed hyperlipidemia 6.
- However, apoB is not measured routinely, and the use of this algorithm may not be widely available 6.
Treatment and Prognosis
- Familial Dysbetalipoproteinemia is highly responsive to therapeutic interventions, including lifestyle modification, such as carbohydrate restriction and calorie restriction, and pharmacotherapy 5.
- Early and correct diagnosis of this condition is necessary to prevent premature vascular disease and other complications 4.