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Familial HDL deficiency
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Reviewed November 2012
What is familial HDL deficiency?
Familial HDL deficiency is a condition characterized by low levels of high-density lipoprotein (HDL) in the blood. HDL is a molecule that transports cholesterol and certain fats called phospholipids through the bloodstream from the body's tissues to the liver. Once in the liver, cholesterol and phospholipids are redistributed to other tissues or removed from the body. HDL is often referred to as "good cholesterol" because high levels of this substance reduce the chances of developing heart and blood vessel (cardiovascular) disease. People with familial HDL deficiency may develop cardiovascular disease at a relatively young age, often before age 50.
Severely reduced levels of HDL in the blood is a characteristic feature of a related disorder called Tangier disease. People with Tangier disease have additional signs and symptoms, such as disturbances in nerve function; enlarged, orange-colored tonsils; and clouding of the clear covering of the eye (corneal clouding). However, people with familial HDL deficiency do not have these additional features.
Read more about Tangier disease.
How common is familial HDL deficiency?
Familial HDL deficiency is a rare disorder, although the prevalence is unknown.
What genes are related to familial HDL deficiency?
Mutations in the ABCA1 gene or the APOA1 gene cause familial HDL deficiency. The proteins produced from these genes work together to remove cholesterol and phospholipids from cells.
The ABCA1 gene provides instructions for making a protein that removes cholesterol and phospholipids from cells by moving them across the cell membrane. The movement of these substances across the membrane is enhanced by another protein called apolipoprotein A-I (apoA-I), which is produced by the APOA1 gene. Once outside the cell, the cholesterol and phospholipids combine with apoA-I to form HDL. ApoA-I also triggers a reaction that converts cholesterol to a form that can be fully integrated into HDL and transported through the bloodstream.
ABCA1 gene mutations and some APOA1 gene mutations prevent the release of cholesterol and phospholipids from cells. Other mutations in the APOA1 gene reduce the protein's ability to stimulate the conversion of cholesterol. These ABCA1 and APOA1 gene mutations decrease the amount of cholesterol or phospholipids available to form HDL, resulting in low levels of HDL in the blood. A shortage (deficiency) of HDL is believed to increase the risk of cardiovascular disease.
How do people inherit familial HDL deficiency?
Familial HDL deficiency is inherited in an autosomal dominant pattern, which means an alteration in one copy of either the ABCA1 or the APOA1 gene in each cell is sufficient to cause the disorder. People with alterations in both copies of the ABCA1 gene develop the related disorder Tangier disease.
Where can I find information about diagnosis or management of familial HDL deficiency?
These resources address the diagnosis or management of familial HDL deficiency and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about familial HDL deficiency?
You may find the following resources about familial HDL deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for familial HDL deficiency?
What if I still have specific questions about familial HDL deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding familial HDL deficiency?
apolipoprotein ; apolipoprotein A-I ; autosomal ; autosomal dominant ; cardiovascular ; cell ; cell membrane ; cholesterol ; deficiency ; familial ; gene ; HDL ; inherited ; lipoprotein ; molecule ; phospholipids ; prevalence ; protein
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (4 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.