Lipodystrophies and complex lipodystrophic syndromes [44 genes]

Lipodystrophies are a heterogeneous group of rare diseases characterized by a partial or generalized absence of adipose tissue and a predisposition to develop metabolic complications that are key to the morbidity and mortality of these patients. These metabolic complications, which include alterations in lipid metabolism (increased triglycerides and decreased HDL), as well as resistance to insulin and diabetes mellitus, are entities associated with increased risk of early atherosclerosis.

Deficiency of adipose mass results in leptin deficiency, leading to hyperfagia and ectopic storage of lipids, in turn causing insulin resistance. Insulin resistance and its associated complications include diabetes mellitus, hypertriglyceridemia, non-alcoholic fatty liver disease, polycystic ovary syndrome, acanthosis nigricans, and early atherosclerosis.

Genetic lipodystrophies include congenital generalized lipodystrophy (CGL) and familial partial lipodystrophy (FPLD). Other systemic disorders associated with lipodystrophy have also been reported, such as lipodystrophy-associated progeroid syndromes and autoinflammatory lipodystrophies.

1. Congenital generalized lipodystrophy: 1-9:1,000,000
2. Familial partial lipodystrophy: 1-9/1,000,000
3. Lipodystrophy-associated progeroid syndromes: unknown
4. Autoinflammatory lipodystrophies: unknown

Genetic testing is useful to identify subtypes of familial lipodystrophies. Moreover, it can help identifying family members at risk, especially for lipodystrophy subtypes associated with subtle physical phenotypes or those with a high risk of morbidity and mortality (e.g. cardiomyopathy and arrhythmias associated with LMNA mutations).

Aimed at patients with suspected congenital generalized lipodystrophy (CGL) or familial partial lipodystrophy (FPLD), according to current clinical criteria, as well as patients with suspected lipodystrophy-associated progeroid syndromes or autoinflammatory lipodystrophies.