Familial Partial Lipodystrophy
Although the most common form of FPL, FPLD2 is a rare genetic disorder that affects the amount and distribution of fat (adipose tissue) in the body. Symptoms typically develop around puberty, after having normal adipose tissue in childhood. FPLD2 causes a loss of adipose tissue from the limbs, torso, buttocks and hips, while causing a buildup of adipose tissue in the face, neck, and upper back. Some people with FPLD2 have areas of dark, thick skin (acanthosis nigricans), and females may have excessive hairiness (hirsutism) and menstrual abnormalities. Metabolic abnormalities develop in adolescence or adulthood, leading to signs and symptoms that may include insulin resistance, dyslipidemia, diabetes, pancreatitis (or recurrent acute pancreatitis), liver steatosis, atherosclerosis, and an increased risk of heart disease.
FPLD2 is caused by mutations in the LMNA gene and inheritance is autosomal dominant. Treatment aims to correct metabolic abnormalities and manage complications. This may involve medications, monitoring the diet, and exercise. Plastic surgery may be considered by some individuals. People with FPL2 are encouraged to seek counseling and support after being diagnosed, as the disorder can cause anxiety and psychological distress. The long-term health outlook generally depends on the severity of complications such as diabetes, pancreatitis, and heart disease.
FPL Type 1, Kobberling Variety (FPL1). This form of FPL has only been reported in a handful of individuals. Affected individuals have normal or slightly increased fat distribution on the face, neck, and trunk. In addition, some affected individuals may develop excess belly fat (central obesity). Metabolic abnormalities including insulin resistance, high blood pressure (hypertension), and severe hypertriglyceridemia have also been reported. This form of FPL has only been reported in women.
FPL Type 3, due to PPARg Mutations (FPL3). This form of FPL has only been reported in approximately 30 individuals. Fat loss is more prominent in the calves and forearms than in the upper arms and thighs. Diabetes, hypertriglyceridemia, hypertension, fatty liver, pancreatitis, and hirsutism have also been reported. Metabolic abnormalities are more prominent than the lipodystrophy in this form of the disorder.
FPL4, due to PLIN1 Mutations (FPL4).This form of FPL has only been reported in a handful of individuals. Lipodystrophy is most prominent in the lower limbs and buttocks. Muscular hypertrophy may be prominent in the calves. Insulin resistance, severe hypertriglyceridemia, and diabetes were also reported.
FPL5, due to AKT2 Mutations (FPL5).This form of FPL has been reported in four members of one family who had hypertension, severe insulin resistance, and diabetes mellitus. Insulin resistance appears around the ages of 20 to 30. Lipodystrophy most prominently affects the arms and legs.
Autosomal Recessive FPL (Type 6 due to CIDEC mutation). This form of FPL has only been reported in one individual in the medical literature. The reported symptoms include partial lipodystrophy, severe insulin resistance, fatty liver, acanthosis nigricans, and diabetes.
More information about FPLD can be found from the NORD (https://rarediseases.org/gard-rare-disease/familial-partial-lipodystrophy/), NIH (https://rarediseases.info.nih.gov/diseases/11962/familial-partial-lipodystrophy)
Mantzoros C. Lipodystrophic syndromes. UpToDate. Waltham, MA: UpToDate; September 14, 2017; https://www.uptodate.com/contents/lipodystrophic-syndromes.
Vigouroux C. Familial partial lipodystrophy, Dunnigan type. Orphanet. February 2015; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2348.
Garg A. Familial Partial Lipodystrophy. National Organization for Rare Disorders (NORD). 2015; http://rarediseases.org/rare-diseases/familial-partial-lipodystrophy/.
LMNA. Genetics Home Reference (GHR). August 2013; https://ghr.nlm.nih.gov/gene/LMNA.