Lipodystrophy

Lipodystrophy is a group of rare disorders characterized by abnormal distribution or loss of adipose tissue. Subtypes are classified by the extent of fat loss (generalized vs partial) and by onset (congenital vs acquired). In generalized forms, nearly all subcutaneous fat is reduced; in partial forms, fat loss is regional and may be accompanied by fat accumulation in other areas. The onset can be present at birth or develop later in life.

Genetic forms include congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, which is caused by mutations in genes such as AGPAT2, BSCL2, CAV1, and PTRF. Familial partial lipodystrophy (FPLD) types are linked to genes including LMNA and PPARG, among others. Acquired lipodystrophy occurs with autoimmune or inflammatory diseases, infections, or HIV-associated antiretroviral therapy.

Pathophysiology involves loss or redistribution of adipose tissue with reduced adipokines, particularly leptin and adiponectin, leading to insulin resistance, hypertriglyceridemia, hepatic steatosis, and other metabolic disturbances. Clinically, patients may exhibit loss of subcutaneous fat from the face, limbs, and buttocks (generalized forms) or regional fat loss in partial forms, often with a lean or muscular appearance and possible fat accumulation in other regions. Metabolic complications frequently drive morbidity, sometimes from early in life.

Diagnosis relies on clinical evaluation supported by imaging and laboratory studies, with genetic testing used to confirm specific forms. Management focuses on controlling metabolic complications and may include leptin replacement therapy for generalized lipodystrophy, as well as diet and exercise, lipid-lowering agents, antihyperglycemic therapies, and regular monitoring for liver disease and cardiovascular risk.