What is Familial Hypobetalipoproteinemia?

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Familial hypobetalipoproteinemia is a rare, inherited condition that causes mild to extremely low LDL cholesterol levels. It mostly occurs due to a mutation in the protein, apolipoprotein b (apoB). This protein is attached to LDL particles and helps transport cholesterol to cells in the body.

There are two types of hypobetalipoproteinemia: homozygous and heterozygous. Individuals who are homozygous for this condition have mutations in both copies of the gene.

Symptoms in these individuals will be more severe and will occur earlier in life, typically within the first 10 years of life. Heterozygous individuals, on the other hand, only have one copy of the mutated gene. Their symptoms are milder, and sometimes, they may not even know that they have this medical condition until their cholesterol is tested during adulthood.

Low levels of cholesterol -– especially LDL cholesterol -– may lower your risk of heart disease. However, if your cholesterol is too low, it could lead to various health complications.

Symptoms of Familial Hypobetalipoproteinemia

The severity of symptoms will depend on which type of familial hypobetalipoproteinemia you have. Individuals with homozygous familial hypobetalipoproteinemia have more severe symptoms than the heterozygous type, which would include:

  • Diarrhea
  • Bloating
  • Vomiting
  • Presence of fatty, pale-colored stools

Besides gastrointestinal symptoms, an infant or child with homozygous hypobetalipoproteinemia displays other symptoms from having very low levels of lipids in the blood, similar to the condition, abetalipoproteinemia.

These symptoms include:

  • Neurological problems. This may be due to low amounts of lipids or fat-soluble vitamins circulating in the body. These symptoms could also include slow development, no deep tendon reflexes, weakness, difficulty walking, and tremors.
  • Problems with blood clotting. This may be due to low vitamin K levels. Red blood cells may also appear abnormal.
  • Vitamin deficiency. Fat-soluble vitamins – A, K, and E – are also very low in these individuals. Lipids are important in transporting fat-soluble vitamins to different areas of the body. When lipids, like cholesterol and triglycerides, are low, they are unable to transport these vitamins where they are needed.
  • Sensory disorders. This includes issues with eyesight and touch sensation.

Individuals with heterozygous hypobetalipoproteinemia may have mild gastrointestinal symptoms, although many have no symptoms.

Both forms of these conditions will have low total and LDL cholesterol levels.

How is Familial Hypobetalipoproteinemia Diagnosed?

A lipid panel will be performed to examine the levels of cholesterol circulating in the blood. A cholesterol test would typically reveal the following findings:


  • Total cholesterol levels < 80 mg/dL
  • LDL cholesterol levels < 20 mg/dL
  • Very low triglyceride levels


  • Total cholesterol levels < 120 mg/dL
  • LDL cholesterol levels < 80 mg/dL
  • Triglyceride levels are usually normal (< 150 mg/dL)

    Levels of apolipoprotein B may be low to nonexistent depending upon the type of hypobetalipoproteinemia present. A biopsy of the liver may also be taken in order to determine whether or not liver disease is contributing to the lowered lipid levels. These factors, in addition to the symptoms the individual is experiencing, will help confirm a diagnosis of familial hypobetalipoproteinemia.

    How is Familial Hypobetalipoproteinemia Treated?

    Treatment of familial hypobetalipoproteinemia depends upon the type of disease. In people with the homozygous type, vitamin supplementation –- especially vitamins A, K, and E –- is important. A dietitian may also be consulted in these cases since a special diet for fat supplementation may need to be implemented.

    In people diagnosed with the heterozygous type of hypobetalipoproteinemia, treatment may not be needed if they are not experiencing any symptoms from the disease. However, some heterozygous individuals may need to be placed on a special diet or receive supplementation with fat-soluble vitamins if symptoms -- such as diarrhea or bloating -- are present.


    Beers MH, Porter RS, Jones TV. Merck Manual of Diagnosis and Therapy. 19th edition, 2011.

    Fauci AC, Kasper DL, Longo DL et al. Harrison’s Principles of Internal Medicine. 18th edition, 2015.

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