Hyperlipidemia type 3

Other Names: Hyperlipoproteinemia type 3; Hyperlipoproteinemia type III; Broad-betalipoproteinemia; Broad beta disease; Familial dysbetalipoproteinemia; Remnant removal disease

Hyperlipidemia type 3 is an inherited condition that disrupts the normal breakdown of fats (lipids) in the body, causing a large amount of certain fatty materials to build up in the body.

Cause

This condition is caused by mutations in the APOE gene. That serves as a ligand for the liver receptor for chylomicrons, IDL and VLDL, also known as very-low-density-lipoprotein receptor. The normal ApoE turns into the defective ApoE2 form due to a genetic mutation. This defect prevents the normal metabolism of chylomicrons, IDL and VLDL, otherwise known as remnants, and therefore leads to accumulation of cholesterol within scavenger cells (macrophages) to enhance development and acceleration of atherosclerosis.

Inheritance

Autosomal recessive inheritance, a 25% chance

The inheritance of this condition is considered to be complicated, as having mutations in the APOE gene often does not lead to the development of symptoms without the influence of other factors. Most people with symptoms of hyperlipidemia type 3 have two mutations in the APOE gene, inherited in an autosomal recessive manner.

Signs and symptoms

Some individuals never have symptoms of this condition. Symptoms usually do not appear unless a second genetic or environmental factor adds to increased lipid levels. Symptoms may include: yellowish lipid-filled bumps on the skin (xanthomas), inflammation of the pancreas (pancreatitis), and a buildup of fat in the blood vessels (atherosclerosis). Hyperlipidemia type 3 may lead to the development of cardiovascular disease.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Decreased HDL cholesterol concentration(Decreased circulating high-density lipoprotein cholesterol)
• Hypercholesterolemia(Elevated serum cholesterol)
• Hypertriglyceridemia(Increased plasma triglycerides)
• Increased LDL cholesterol concentration(Increased circulating LDL level)

30%-79% of people have these symptoms

• Corneal arcus
• Diabetes mellitus
• Hepatic steatosis(Fatty infiltration of liver)
• Hepatomegaly(Enlarged liver)
• Obesity(Having too much body fat)
• Tendon xanthomatosis
• Type IV atherosclerotic lesion
• Xanthelasma(Fatty deposits in skin around the eyes)

5%-29% of people have these symptoms

• Accelerated atherosclerosis
• Acute pancreatitis(Acute pancreatic inflammation)
• Angina pectoris
• Aortic atherosclerotic lesion
• Gout
• Hypothyroidism(Underactive thyroid)
• Peripheral arterial stenosis
• Premature coronary artery atherosclerosis(Premature coronary artery disease)
• Renal steatosis(Fatty kidney)

Diagnosis

Tests that may be done to diagnose this condition include:

• Genetic testing for apolipoprotein E (apoE)
• Lipid panel blood test
• Triglyceride level
• Very low density lipoprotein (VLDL) test

Treatment

The goal of treatment is to control conditions such as obesity, hypothyroidism, and diabetes. Making diet changes to reduce calories, saturated fats, and cholesterol may help lower blood cholesterol. If cholesterol and triglyceride levels are still high after you have made diet changes, your health care provider may have you take medicines as well. Medicines to lower blood triglyceride and cholesterol levels include:

• Bile acid-sequestering resins.
• Fibrates (gemfibrozil, fenofibrate).
• Nicotinic acid.
• Statins.
• PCSK9 inhibitors, such as alirocumab (Praluent) and evolocumab (Repatha). These represent a newer class of drugs to treat cholesterol.

Prognosis

People with this condition have a significantly increased risk for coronary artery disease and peripheral vascular disease. With treatment, most people are able to greatly reduce their levels of cholesterol and triglycerides.

Possible Complications Complications may include:

• Heart attack
• Stroke
• Peripheral vascular disease
• Intermittent claudication
• Gangrene of the lower extremities

NIH genetic and rare disease info

• NIH info on Hyperlipidemia type 3

Hyperlipidemia type 3 is a rare disease.