Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)

Familial hypobetalipoproteinemia

Synonym(s) -
Prevalence >1 / 1000
Inheritance -
Age of onset All ages
  • E78.6
  • C1862596
MeSH -
MedDRA -


Familial hypobetalipoproteinemia is the familial form of hypobetalipoproteinemia (see this term), which is characterized by permanently low levels (below the 5th percentile) of apolipoprotein B and LDL cholesterol.

It affects 1/1,000 individuals and therefore is not rare in Europe.

Familial hypobetalipoproteinemia can be severe with early onset (abetalipoproteinemia/ homozygous familial hypobetalipoproteinemia; see this term) or benign (benign familial hypobetalipoproteinemia). Severe early familial hypobetalipoproteinemia manifests in infancy or childhood. It is often associated with growth delay, diarrhea with steatorrhea, and fat malabsorption. Spastic ataxia, atypical retinitis pigmentosa, acanthocytosis, a low level of liposoluble vitamins (A, E, K), and major cytolysis and even cirrhosis can occur. Benign familial hypobetalipoproteinemia is generally asymptomatic, but in adults it is occasionally associated with a dietary intolerance to fat, steatorrhea after oral lipid intake, moderate cytolysis, cholelithiasis, a moderately low level of liposoluble vitamins and acanthocytosis. Moderate hepatic steatosis and paresthesia of the extremities are sometimes observed.

Abetalipoproteinemia is a result of mutations of two alleles of the MTTP gene (MTP; 4q24). Other severe early familial hypobetalipoproteinemias are a result of mutations of two alleles of the APOB gene (2p24-p23). Benign familial hypobetalipoproteinemia can be caused by heterozygous mutations of the APOB gene or the PCSK9 gene (1p34.1-p32).

Diagnosis of familial hypobetalipoproteinemia is based on lipid analysis, after 12 hours of fasting, carried out on the patient and their parents to measure serum levels of LDL (<0.10g/L for the severe form; <0.80g/L for the moderate form), triglycerides (<0.20 g/L for the severe form; <0.50g/L for the moderate form), and apolipoprotein B (<0.10g/L for the severe form; <0.50g/L for the moderate form). Identification of steatorrhea and truncated apolipoprotein B after oral lipid intake, measurement of liposoluble vitamins (A, E, K), tests for acanthocytosis (on blood smears), complete neurological examination, hepatic ultrasound and eye examination can also be carried out. Identification of mutations in the MTTP, APOB or PCSK9 genes confirms the diagnosis.

Differential diagnoses of severe early familial hypobetalipoproteinemia include metabolic diseases with hepatic overload, with steatosis and/or hepatomegaly, atypical diseases of the central and peripheral nervous system, and secondary causes of hypocholesterolemia (iatrogenic or systemic).

Prenatal diagnosis is feasible when the causal mutations in both parents are known.

Abetalipoproteinemia is inherited in a recessive manner. Other severe early familial hypobetalipoproteinemias are inherited in a codominant manner. Benign familial hypobetalipoproteinemia, is also inherited in a codominant manner.

Management of the moderate form includes reduction of the proportion of fat in the patient's diet and vitamin E supplementation. Management of the severe form is done in specialized centers.

The prognosis of familial hypobetalipoproteinemia is severe when the disease manifests in early childhood, and is excellent for the moderate form without cytolysis and steatosis. A familial syndrome of longevity has been observed in the benign forms (many patients live over the age of 85).

Expert reviewer(s)

  • Dr Pascale BENLIAN

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Guidance for genetic testing
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.