Does Familial Type 3 Hyperlipoproteinemia indicate metabolic dysfunction?

From the Guidelines

Familial Type 3 Hyperlipoproteinemia is a genetic disorder that indicates metabolic dysfunction, characterized by impaired clearance of chylomicron and VLDL remnants from the bloodstream due to a defect in apolipoprotein E (apoE). This condition leads to elevated levels of both cholesterol and triglycerides in the blood, typically in the range of 300-600 mg/dL for each, and is often inherited in an autosomal recessive pattern 1. The metabolic dysfunction in this disorder is exacerbated by other metabolic factors like obesity, diabetes, or hypothyroidism, which can become clinically apparent in adulthood 1.

Some key features of Familial Type 3 Hyperlipoproteinemia include:

• Elevated levels of cholesterol and triglycerides in the blood
• Impaired clearance of chylomicron and VLDL remnants from the bloodstream due to a defect in apolipoprotein E (apoE)
• Autosomal recessive inheritance pattern
• Often becomes clinically apparent in adulthood, particularly when other metabolic factors like obesity, diabetes, or hypothyroidism are present
• Patients may develop characteristic orange-yellow deposits called tuberous xanthomas on their elbows and knees, as well as palmar xanthomas in the creases of their hands

The metabolic dysfunction in this disorder significantly increases the risk of premature atherosclerosis and cardiovascular disease, particularly in the peripheral arteries 1. According to a study published in Circulation, 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.

In terms of management, recommendations similar to those for managing combined hyperlipidemia apply, including dietary therapy and attention to other lifestyle factors 1. The use of drug therapy, such as fibrates and nicotinic acid, may also be considered in some cases 1. However, it is essential to note that the management of Familial Type 3 Hyperlipoproteinemia should be individualized and based on the specific needs and circumstances of each patient.

From the Research

Metabolic Dysfunction in Familial Type 3 Hyperlipoproteinemia

• Familial Type 3 Hyperlipoproteinemia, also known as dysbetalipoproteinemia, is a genetic disorder characterized by elevated levels of cholesterol and triglycerides in the blood 2, 3.
• This condition is often associated with metabolic syndrome, a cluster of conditions that increase the risk of developing type 2 diabetes and cardiovascular disease 4.
• Studies have shown that individuals with Familial Type 3 Hyperlipoproteinemia are at a higher risk of developing metabolic dysfunction, including insulin resistance and diabetes mellitus 4.
• The presence of metabolic syndrome in individuals with Familial Type 3 Hyperlipoproteinemia is often characterized by high plasma remnant lipoproteins, high triglyceride levels, and low HDL cholesterol levels 4.
• The interplay between lipid and glucose metabolism in Familial Hypercholesterolemia, a related condition, suggests that diabetes may modify the phenotype of the disease, affecting both the lipid profile and cardiovascular risk 5.

Clinical Features and Diagnosis

• The clinical features of Familial Type 3 Hyperlipoproteinemia include tuberoeruptive xanthomas, palmar xanthomas, and premature vascular disease 2, 3.
• The diagnosis of Familial Type 3 Hyperlipoproteinemia is often made using a combination of clinical features, laboratory tests, and genetic analysis 2, 3.
• Beta quantification, which measures the presence of "β-VLDL" in the supernatant following ultracentrifugation, is considered a definitive biochemical test for the disease 3.
• Apolipoprotein B testing may also be used as an initial test to select patients for further investigation, due to its relatively low cost and wide availability 3.

Association with Metabolic Dysfunction

• The association between Familial Type 3 Hyperlipoproteinemia and metabolic dysfunction is well established, with many individuals with the condition also having metabolic syndrome 4.
• The presence of metabolic syndrome in individuals with Familial Type 3 Hyperlipoproteinemia increases the risk of developing cardiovascular disease and type 2 diabetes 4.
• Further research is needed to fully understand the interplay between lipid and glucose metabolism in Familial Type 3 Hyperlipoproteinemia and to develop effective treatments for metabolic dysfunction in individuals with the condition 5.