National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Familial hypobetalipoproteinemia


Other Names:
Hypobetalipoproteinemia, familial; FHBL
Subtypes:
Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats, causing low levels of cholesterol in the blood. The severity of the condition varies widely. Mildly affected people may have no signs or symptoms. Many affected people develop an abnormal buildup of fats in the liver (called hepatic steatosis, or fatty liver). In severe cases, this may progress to cirrhosis. Some people also have digestive problems in childhood, resulting in failure to thrive. FHBL is usually caused by mutations in the APOB gene. In a few cases, it may be caused by mutations in other genes, or the cause may be unknown. It is inherited in an autosomal codominant manner; a mutation in one copy of the APOB gene can cause the condition, but changes in both copies of the gene cause more severe symptoms.[1] Management may include reducing fat in the diet and vitamin E supplementation.[2]
Last updated: 6/9/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Rod-cone dystrophy 0000510
Percent of people who have these symptoms is not available through HPO
Acanthocytosis 0001927
Ataxia 0001251
Autosomal recessive inheritance 0000007
Decreased LDL cholesterol concentration 0003563
Reduced tendon reflexes 0001315
Retinal degeneration
Retina degeneration
0000546
Showing of 7 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.
The long-term outlook (prognosis) for people with familial hypobetalipoproteinemia (FHBL) can vary considerably. Because it is usually inherited in a codominant manner, a mutation in one copy of the APOB gene can cause the condition, but changes in both copies of the gene can cause more severe symptoms. A person with one mutated copy of the gene is referred to as a heterozygote; a person with 2 mutated copies of the gene is referred to as a homozygote. Furthermore, severity and symptoms in each person can depend on the specific mutation(s) in the gene that each affected person has.[3][4]

Most people with FHBL are heterozygotes and are generally asymptomatic, but may develop fatty liver.[3] Progression to steatohepatitis (a swollen liver that can cause cirrhosis over time) or the development of other complications is uncommon.[4] To date, only a few case reports linking heterozygotes and severe liver diseases have been published.[3] A few FHBL heterozygotes may have loose stools due to partial fat malabsorption.[5] In some families with a mild (benign) form, longevity has been observed, with many affected people living past the age of 85. Generally, for people with a mild or moderate form of FHBL who do not have destruction of liver cells or fatty liver, the prognosis is very good.[2]

Homozygotes with FHBL are much more rare, and signs and symptoms vary. Some people are asymptomatic or have mild fatty liver disease, while others have severe hepatic steatosis (swelling), intestinal fat malabsorption, failure to thrive, and/or neurological and ocular (eye) dysfunctions.[3] If left untreated, adults can develop retinal degeneration and/or cerebellar dysfunction resulting in ataxia and loss of sensory ability and deep tendon reflexes.[3] Severe vitamin E deficiency is reportedly responsible for the development of neurological symptoms.[4] The development of cirrhosis has been seen in both adulthood and early infancy.[3] Generally, the prognosis is severe when the condition manifests in early childhood.[2]

People with specific questions about how FHBL may affect themselves or family members should speak with a liver specialist or other health care provider.
Last updated: 6/10/2015
Familial hypobetalipoproteinemia (FHBL) is estimated to occur in more than 1 in 1000 people in Europe.[2] Some sources report that in the United States, the heterozygous form affects about 1 in 500, while the homozygous form affects about 1 in 1 million. The international frequency is thought to be similar.[6]
Last updated: 6/10/2015

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Familial hypobetalipoproteinemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Familial hypobetalipoproteinemia. This website is maintained by the National Library of Medicine.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Familial hypobetalipoproteinemia. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Familial hypobetalipoproteinemia. Genetics Home Reference (GHR). August 2012; http://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia.
  2. Benlian P. Familial hypobetalipoproteinemia. Orphanet. May 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=426.
  3. Cefalù AB, et. al. Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature. Atherosclerosis. March, 2015; 239(1):209-217.
  4. Lam MC, Singham J, Hegele RA, Riazy M, Hiob MA, Francis G, Steinbrecher UP. Familial hypobetalipoproteinemia-induced nonalcoholic steatohepatitis. Case Rep Gastroenterol. May, 2012; 6(2):429-437.
  5. Schonfeld G. Familial hypobetalipoproteinemia: a review. J Lipid Res. May, 2003; 44(5):878-883.
  6. Vibhuti N Singh. Low LDL Cholesterol (Hypobetalipoproteinemia). Medscape. December 16, 2014; http://emedicine.medscape.com/article/121975-overview#a0199.