Familial HDL Deficiency

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Familial HDL Deficiency is caused by a problem in the ABCA1 gene or the APOA1 gene. These genes produce separate proteins that work together to create HDL (high density lipoprotein). HDL transports cholesterol and other fats called phospholipids through the bloodstream around the body. This process is important because HDL is considered to be “good” cholesterol that significantly reduces heart problems. 

If you have a problem in the ABCA1 or APOA1 genes, you will not produce enough HDL. Therefore, you will be unable to transport the “good” cholesterol around your body, which causes early-onset heart and cardiovascular disease. 

Familial HDL Deficiency is very rare, so it is difficult to determine how many people are affected. However, around 30 families have reportedly been identified with the disorder. 

 Due to the small amount of people diagnosed, it is not possible to suggest whether the disorder is more likely to affect any specific group, ethnicity, race, or gender.  

The age at which the symptoms of Familial HDL Deficiency begin to show can vary from person to person. You may have symptoms in adolescence, but some people will not show any signs of the disorder until they are well into adulthood. Symptoms include: 

•  Blurred vision 
• Raised fatty bumps on the skin that are typically yellow, but can also appear orange, red, or brown in colour (known as xanthomas). They may cover a large area and can appear in many places on the body. They can appear very suddenly, depending on the type of manifestation 
• Small yellowish marks on or around the eyelids (xanthelasmas) 
• Developing cardiovascular disease at a young age (under 50) 
• Heart attack and/or stroke 

You may experience hearing loss and issues with your balance, coordination and speech. Some cases of Familial HDL Deficiency have also reported multiple organ failure. 

 Life expectancy for the disorder is uncertain due to the very small amount of cases reported. Typically, it depends upon the severity of your symptoms, particularly in relation to any heart and organ problems. 

Familial HDL Deficiency is diagnosed using a specialised blood test. Your medical team may also carry out a skin biopsy, particularly if you present with xanthomas. This is usually done under local anaesthetic.  

 The disorder may initially be mistaken for Tangier disease or LCAT deficiency. Extremely low HDL cholesterol levels may also be caused by medications (such as steroids and fibrates) and the presence of tumours, so your medical team may want to consider these possibilities before diagnosing Familial HDL Deficiency. 

 This disorder may not show any symptoms until well into adulthood, and so it is important to consult your medical team if any of your immediate family, such as parents, children, or siblings, receive a diagnosis. It may be the case that you also need to undergo medical tests. 

 Currently, Familial HDL Deficiency is not detected as part of newborn screening in any country. However, if there is evidence that this disorder is severe and life-limiting within the family, antenatal testing may be offered. 

Treatment for Familial HDL Deficiency works to reduce the severity of the symptoms. There is currently no cure.  

Your medical team will recommend a low-fat diet to reduce the risk of serious heart and circulatory problems, including premature cardiovascular disease. You may also be prescribed medication to lower your cholesterol. It is important you follow the advice given to you to ensure that any symptoms you experience can be managed appropriately.  

Should you wish to make changes to your diet or lifestyle, consult a specialist dietician beforehand to ensure that any changes will not have a negative impact on your health. 

If you develop premature cardiovascular disease or organ failure, you may require other treatments, including inpatient hospital care and, in some cases, surgery. 

The prognosis for Familial HDL Deficiency depends on whether you develop premature cardiovascular disease or organ failure. Some people, with the correct diet and treatment, have a very good outcome and can live a healthy life. However, more serious cases of the disorder may result in a reduced lifespan. 

Familial HDL Deficiency is inherited from either parent in an autosomal dominant inheritance pattern. This means that only one parent has to be affected to pass on the disorder through their genes.  

 All genes come in pairs. People with Familial HDL Deficiency have one working gene and one faulty gene. This is either the ABCA1 gene or the APOA1 gene.  

 Children inherit one gene from each parent to make their pair. If one parent has Familial HDL Deficiency: 

 There is a 50% chance that the child will inherit one faulty and one working gene, which means they will also have Familial HDL Deficiency. 

• There is a 50% chance that the child will inherit two working genes and not inherit the disorder. 

Familial HDL Deficiency occurs when one of the two genes is faulty. It is important to note that if you inherit two faulty ABCA1 genes, then you will develop Tangier Disease instead. 

If you think somebody in your immediate family, such as your parents, siblings, or children, may have Familial HDL Deficiency, contact your medical team who may refer you for genetic testing.

References are available on request. Please contact us by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No: AAP002].