lipodystrofian

Lipodystrophy refers to a group of rare disorders characterized by abnormal distribution or loss of adipose tissue. In generalized forms, subcutaneous fat is markedly reduced or absent from most of the body; in partial forms, fat loss occurs in specific regions with relative fat accumulation in others such as the face or abdomen. Lipodystrophies can be congenital (present at birth) or acquired later in life, and they may affect the whole body or only certain areas.

Most inherited lipodystrophies are caused by mutations in genes involved in adipocyte development and lipid storage. Examples include congenital generalized lipodystrophy caused by mutations in AGPAT2 or BSCL2, and familial partial lipodystrophies due to mutations in LMNA, PPARG, AKT2, among others. Acquired forms can be associated with autoimmune diseases or with HIV treatment (antiretroviral–related lipodystrophy). The underlying pathophysiology typically involves loss or dysfunction of fat cells leading to ectopic fat deposition in organs such as the liver and muscle, contributing to metabolic complications.

Clinical features include abnormal fat distribution with insulin resistance, diabetes or impaired glucose tolerance, hypertriglyceridemia, and hepatic steatosis. In generalized forms, metabolic problems may appear early in life; in partial forms, they vary with the pattern of fat loss.

Diagnosis relies on clinical assessment, family history, metabolic evaluation, and genetic testing to identify mutations. Imaging, such as DEXA, can quantify fat loss and help differentiate from obesity. Management focuses on controlling metabolic complications through lifestyle measures, lipid and glucose-lowering therapies, and, in eligible patients, metreleptin therapy to address leptin deficiency. Regular monitoring for liver disease, pancreatitis, and cardiovascular risk is advised.

Prognosis varies with the extent of fat loss and associated metabolic disease; lipodystrophy remains a rare and heterogeneous condition.