Familial hypobetalipoproteinemia

Title

Other Names:

Hypobetalipoproteinemia, familial; FHBL

Summary Summary

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

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Rod-cone dystrophy	5%
Acanthocytosis	-
Ataxia	-
Autosomal recessive inheritance	-
Hypobetalipoproteinemia	-
Retinal degeneration	-

Last updated: 9/1/2016

Diagnosis Diagnosis

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.

Prognosis Prognosis

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

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Research Research

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 studying or have studied Familial hypobetalipoproteinemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.
Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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

Children's Liver Disease Foundation
36 Great Charles Street
Birmingham, B3 3JY
United Kingdom
Telephone: +44 (0) 121 212 3839
Fax: +44 (0) 121 212 4300
E-mail: info@childliverdisease.org
Website: http://www.childliverdisease.org/

Organizations Providing General Support

American Association for the Study of Liver Diseases
1001 North Fairfax, Suite 400
Alexandria, VA 22314
Telephone: 703–299–9766
Fax: 703–299–9622
E-mail: aasld@aasld.org
Website: http://www.aasld.org/
American Liver Foundation
39 Broadway, Suite 2700
New York, NY 10006
Toll-free: 800-465-4837
E-mail: info@liverfoundation.org
Website: http://www.liverfoundation.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

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.

Related Diseases Related Diseases

The following diseases are related to Familial hypobetalipoproteinemia. If you have a question about any of these diseases, you can contact GARD.

Abetalipoproteinemia

GARD Answers GARD Answers

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I was diagnosed with hypobetalipoproteinemia when I was born. I haven't seen anyone about the condition since I was a teenager and I'm now 26 and I was wondering how it can affect me as I get older. I know bits and pieces but would like to know more. I'm also interested to know how many people there are that have this condition in the UK and world. See answer

Have a question? Contact a GARD Information Specialist.

References References

Familial hypobetalipoproteinemia. Genetics Home Reference (GHR). August 2012; http://ghr.nlm.nih.gov/condition/familial-hypobetalipoproteinemia.
Benlian P. Familial hypobetalipoproteinemia. Orphanet. May 2009; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=426.
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.
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.
Schonfeld G. Familial hypobetalipoproteinemia: a review. J Lipid Res. May, 2003; 44(5):878-883.