From the Guidelines
Familial type 3 hyperlipoproteinemia, also known as dysbetalipoproteinemia, is a genetic disorder characterized by the accumulation of cholesterol-rich VLDL, resulting in elevated levels of cholesterol and triglycerides in the blood, with a characteristic ratio of core CE to triglyceride of 0.3, and is often associated with impaired receptor-mediated clearance and increased VLDL hepatic production. This condition is due to a defect in apolipoprotein E (apoE), specifically the apoE2 isoform, which displays defective binding to the LDL receptor compared with the most common apoE3 isoform 1. The type III phenotype is often characterized by near-equivalent cholesterol and triglyceride values, and apo B is not a useful marker of overall atherogenicity, as in FCHL; non–HDL-C would be a more appropriate target 1.
Key Characteristics
- Elevated levels of cholesterol and triglycerides in the blood
- Characteristic ratio of core CE to triglyceride of 0.3
- Impaired receptor-mediated clearance and increased VLDL hepatic production
- Often associated with palmar or tuboeruptive xanthomas and increased cardiovascular and peripheral vascular disease risk
- Affected individuals may be extraordinarily responsive to a low-carbohydrate diet
Diagnosis and Treatment
Diagnosis involves lipid profile testing showing elevated total cholesterol and triglycerides with a characteristic ratio, genetic testing for apoE variants, and sometimes lipoprotein electrophoresis 1. Treatment focuses on lifestyle modifications including a low-fat diet, regular exercise, weight management, and avoiding alcohol and simple carbohydrates. Medications such as statins and fibrates are often prescribed to lower lipid levels 1.
Inheritance and Prevalence
The condition is inherited in an autosomal recessive pattern, requiring two defective copies of the apoE gene, and is relatively rare, affecting approximately 1 in 10,000 people 1. However, the exact prevalence may vary depending on the population and other factors.
From the Research
Definition and Characteristics
- Familial type 3 hyperlipoproteinemia, also known as familial dysbetalipoproteinemia, is a highly atherogenic dyslipoproteinemia characterized by hypercholesterolemia and hypertriglyceridemia due to markedly increased numbers of cholesterol-enriched chylomicron and very-low-density lipoprotein (VLDL) remnant lipoprotein particles 2, 3, 4.
- This condition is typically associated with homozygosity for the apolipoprotein E2 isoform, but also sometimes with dominant rare missense variants in the APOE gene 5.
- Patients with type 3 hyperlipoproteinemia often present with roughly equimolar elevations of cholesterol and triglyceride due to pathologic accumulation of remnant lipoprotein particles 5.
Clinical Features
- Clinical features of type 3 hyperlipoproteinemia include tuberoeruptive xanthomas, palmar xanthomas, and premature vascular disease 6, 5.
- Patients with this condition are also at increased risk of developing diabetes mellitus, metabolic syndrome, and coronary heart disease 2.
- The mean age at diagnosis of the disorder is around 49-53 years, with a high prevalence of obesity, xanthomas, and atherosclerosis, especially peripheral vascular disease 6.
Diagnosis
- Diagnosis of type 3 hyperlipoproteinemia can be made based on a simple diagnostic algorithm, which involves total cholesterol, triglycerides, and apolipoprotein B (apoB) 4.
- High plasma remnant lipoprotein cholesterol (RLP-C) levels above 30 mg/dL and high plasma RLP-C/plasma triglyceride ratio above 0.1 are very useful for diagnosis of type 3 hyperlipoproteinemia 2.
- However, apoB is not measured routinely, and unless apoB is introduced into routine clinical care, type 3 hyperlipoproteinemia will often not be recognized 4.
Treatment and Management
- Type 3 hyperlipoproteinemia is strongly associated with atherosclerosis and responds well to therapeutic interventions, including lifestyle modification, especially carbohydrate restriction and calorie restriction, and pharmacotherapy 3.
- Early and correct diagnosis of this familial lipoprotein disorder seems necessary because of the prompt and beneficial response to therapeutic interventions 6.