What are the other Names for this Condition? (Also known as/Synonyms)

• Familial High Density Lipoprotein Deficiency Disorder
• Familial Hypoalphalipoproteinemia (FHA)
• Primary Hypoalphalipoproteinemia

What is Familial HDL Deficiency Disorder? (Definition/Background Information)

• Familial HDL Deficiency Disorder is a rare genetic condition that causes low levels of "good" cholesterol (HDL) in the blood. HDL helps remove excess cholesterol and fats from your blood
• People with Familial HDL Deficiency may develop cardiovascular disease at a relatively young age, often before age 50
• This condition is caused by changes in the ABCA1 or the APOA1 genes. The deficiency is passed through families in an autosomal dominant pattern

(Source: Familial HDL Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Familial HDL Deficiency Disorder? (Age and Sex Distribution)

• Familial HDL Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur at any age
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Familial HDL Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Familial HDL Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial HDL Deficiency Disorder? (Etiology)

• Familial HDL Deficiency Disorder is caused by changes in the ABCA1 or the APOA1 genes
  • The ABCA1 gene codes for a protein that facilitates the transport of molecules such as cholesterol and phospholipids across cell membranes, and is found in abundance in the liver and macrophages
  • The APOA1 gene codes for apolipoprotein A-1. The cholesterol and phospholipids transported by ABCA1 protein are picked up by APOA1 protein, and in combination with those molecules forms the HDL
• Familial HDL Deficiency Disorder is inherited in an autosomal dominant manner

Autosomal dominant mode of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Familial HDL Deficiency Disorder?

The signs and symptoms of Familial HDL Deficiency Disorder may include:

• Very frequently present symptoms in 80-99% of the cases include lymphadenopathy
• Frequently present symptoms in 30-79% of the cases:
  • Abnormality of the liver
  • Anemia
  • Blurred vision
  • Corneal opacity
  • Decreased circulating high-density lipoprotein levels
  • EMG abnormality
  • Hemiplegia/hemiparesis
  • Splenomegaly
  • Xanthomatosis

(Source: Familial HDL Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Other signs and symptoms also include:

• Neurosensory hearing loss
• Cerebellar ataxia
• Hepatomegaly
• Nephropathy
• Cardiomyopathy

(Source: Apolipoprotein A-1 deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is Familial HDL Deficiency Disorder Diagnosed?

Familial HDL Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for, or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial HDL Deficiency Disorder?

The complications of Familial HDL Deficiency Disorder may include:

• Deafness
• Proliferative retinopathy, which may lead to severely impaired vision
• Signs of secondary amyloidosis
• Liver failure
• End-stage kidney disease
• Myocardial infarction

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Familial HDL Deficiency Disorder Treated?

There is no cure for Familial HDL Deficiency Disorder, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. The treatment may include:

• Recommendations for a low-fat diet
• Statins to help keep the LDL (low density lipoprotein) cholesterol below levels that can harm the heart and other organs

How can Familial HDL Deficiency Disorder be Prevented?

Familial HDL Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited disorders such as Familial HDL Deficiency Disorder
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Familial HDL Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Familial HDL Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Familial HDL Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/