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

• FPLD (Familial Partial Lipodystrophy)

What is Familial Partial Lipodystrophy? (Definition/Background Information)

• Familial Partial Lipodystrophy (FPLD) is a group of diseases characterized by an abnormal distribution of fat around the body. Specifically, fat is lost in the arms, legs, and hips, and gained around the face and liver
• Symptoms usually develop around puberty and include problems breaking down food and resistance to the hormone that helps control blood sugar (insulin). Insulin resistance can eventually lead to diabetes 
• Other symptoms may include inflammation of the pancreas (pancreatitis), heart problems, and high blood pressure (hypertension). There are at least six subtypes of Familial Partial Lipodystrophy. The most common form is type 2
• Familial Partial Lipodystrophy can be caused by a change (mutation) in one of several genes. These genes are responsible for making proteins that play an important role in fat storage
• Familial Partial Lipodystrophy can be inherited in an autosomal dominant or autosomal recessive manner
• Treatment may require a team of specialists who can monitor the patient for any health changes and prescribe a special diet and medication to treat the symptoms of the disease

(Source: Familial Partial Lipodystrophy; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Familial Partial Lipodystrophy? (Age and Sex Distribution)

• Familial Partial Lipodystrophy is a rare congenital disorder. The presentation of symptoms generally occurs at the time of puberty
• 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 Partial Lipodystrophy? (Predisposing Factors)

• A positive family history may be an important risk factor, since Familial Partial Lipodystrophy can be inherited
• Currently, no other risk factors have been clearly identified for the 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 Partial Lipodystrophy? (Etiology)

• The exact cause of Familial Partial Lipodystrophy type 1 is not known at the present time
• The most common subtype of Familial Partial Lipodystrophy is type 2, and is caused by mutation(s) in the LMNA gene
• In addition, mutation(s) in PPARG, AKT2 & PLIN1, CIDEC, and LIPE genes have also been reported to respectively cause subtypes 3, 4, 5 and 6 of Familial Partial Lipodystrophy
• The causative gene mutations lead to impaired and abnormal fat storage, leading to the characteristic symptoms of the disorder
• Both autosomal dominant and autosomal recessive patterns of inheritance have been reported for FPLD

Autosomal dominant: 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.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Familial Partial Lipodystrophy?

The signs and symptoms of Familial Partial Lipodystrophy may include:

• Loss of fat tissue from limbs, trunk and buttocks
• Prominence of veins in legs
• Accumulation of fat in the face and neck
• Insulin resistance
• Pancreatitis
• Hepatic steatosis
• Acanthosis nigricans
• High blood pressure

Signs and symptoms of Familial Partial Lipodystrophy specific to women include:

• Hirsutism
• Disturbed menstrual cycles (oligomenorrhea)
• Cysts in ovaries (polycystic ovaries)

How is Familial Partial Lipodystrophy Diagnosed?

Familial Partial Lipodystrophy 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

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 Partial Lipodystrophy?

The complications of Familial Partial Lipodystrophy may include:

• Recurrent bouts with pancreatitis
• Hepatic steatosis leading to liver cirrhosis
• Diabetes (and associated complications)
• Increased risk for coronary heart diseases
• Infertility in women

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

How is Familial Partial Lipodystrophy Treated?

There is no cure for Familial Partial Lipodystrophy, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Familial Partial Lipodystrophy be Prevented?

Familial Partial Lipodystrophy 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 and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Familial Partial Lipodystrophy? (Outcomes/Resolutions)

• The prognosis of Familial Partial Lipodystrophy 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
• Complications, such as high blood pressure and coronary heart diseases, may lead to cardiac arrests and fatalities
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Familial Partial Lipodystrophy:

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

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