Familial Partial Lipodystrophy (FPL)

What is FPL?

Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by progressive loss of body fat from various parts of the body. This body fat – adipose tissue – is found in many parts of the body, including beneath the skin and surrounding the internal organs (subcutaneous fat). Those with familial FPL lose the adipose tissue from their arms, legs, and hips – and the fat then accumulates around the face, neck, and inside the abdomen. This excess fat gives individuals an appearance described as “cushingoid,” because it resembles the physical features associated with Cushing disease. In most cases, this fat loss begins during puberty. FPL can be associated with a variety of metabolic abnormalities. The extent of the adipose tissue loss often determines the severity of metabolic complications, including glucose intolerance and elevated levels of triglycerides in the blood. Six subtypes of FPL have been identified, with each type caused by a distinct gene mutation:

• FPL Type 1, Kobberling Variety (FPL1)
• FPL Type 2, Dunnigan Variety (FPL2)
• FPL Type 3, due to PPARG Mutations (FPL3)
• FPL4, due to PLIN1 Mutations (FPL4)
• FPL5, due to AKT2 Mutations (FPL5)
• Autosomal Recessive FPL (Type 6 due to CIDEC mutation)

An estimated 1 in 1 million people have FPL, but because of misdiagnoses and non-diagnoses, that number is likely higher. It has been reported in women more than in men, and has higher incidence in individuals of African and Indian descent.

What are the symptoms of FPL?

Symptoms largely depend on the different subtype of FPL, but generally include:

• Selective, progressive loss of subcutaneous fat in the arms and legs and chest and trunk regions
• Abnormal accumulation of subcutaneous fat in other areas
• Liver issues
• Heart issues
• pancreatitis
• Diabetes

Furthermore, those with FPL may have a variety of metabolic complications including:

• Insulin resistance
• High blood pressure
• Hypertriglyceridemia

What causes FPL?

FPL is a genetic disorder. It is caused by mutations of specific genes, depending on the type of FPL. So far, mutations in five genes have been identified:

• the LMNA gene, which causes FPL2 and the Dunnigan variety
• the PPARG gene, which causes FPL3
• the PLIN1 gene, which causes FPL4
• the AKT2 gene, which causes FPL5
• the CIDEC gene, which causes autosomal recessive FPL

The gene that causes FPL1 has yet to be identified. Some with FPL do not have mutations in these genes, suggesting that yet-to-be-indentified genes can cause FPL.

How is FPL diagnosed?

FPL is diagnosed based on symptoms, patient history, and a thorough clinical evaluation. Exams include:

• A blood chemical profile
• MRI
• Molecular genetic testing
• Hormones evaluation

What treatments are available for FPL?

There is currently no approved pharmacotherapy in the United States to treat FPL at large, only its individual symptoms. These include fibric acid derivatives, statins, or n-3 polyunsaturated fatty acids for hypertriglyceridemia and insulin for diabetes, etc. Those with FPL should maintain a high carb, low-fat diet.  Regular exercise is also encouraged.

Where can I learn more about FPL?

• NIH
• National Organization for Rare Disorders (NORD)
• Mayo Clinic