In generalised lipodystrophies, the loss of subcutaneous fatty tissue affects the entire body, whereas in partial forms only parts of the body are affected. There are four main categories: congenital generalised lipodystrophy (CGL), familial partial lipodystrophy (FPL), acquired generalised lipodystrophy (AGL) and acquired partial lipodystrophy (APL).

Some causative genetic changes (mutations) have already been identified for the congenital forms. However, the cause of a large proportion of genetic lipodystrophies is still unknown. Acquired lipodystrophy can have various causes, such as immunological disorders, infections or the administration of certain drugs, in particular antiretroviral drugs as part of HIV therapy or insulin.

Due to their rarity and their great clinical heterogeneity and correspondingly variable symptoms, lipodystrophies are difficult to diagnose and are often only recognised very late. Lipodystrophies can be diagnosed by precisely analysing the clinical phenotype and, if necessary, by genetic testing. For a large proportion of patients, regular annual examinations for secondary diseases are recommended.

Lipodystrophies are often associated with hormonal and metabolic changes that can lead to severe metabolic complications. These depend on the subtype of lipodystrophy, the extent of adipose tissue loss, age and gender. Due to the lack of adipose tissue, patients often suffer from a deficiency of the hormoneleptin. Leptin is produced in adipose tissue and plays a central role in energy homeostasis as well as fat and glucose metabolism. Leptin deficiency leads to metabolic and hormonal disorders, loss of fat under the skin and fat accumulation in the liver (up to fatty liver), in the muscles and in the blood (hypertriglyceridaemia). Furthermore, insulin resistance can occur with increased blood glucose levels, which can result in diabetes mellitus that is difficult to treat. The regulation of satiety can be disturbed, which can lead to hyperphagia (increased food intake due to a lack of satiety) and thus increased calorie intake. Excess fatty acids are deposited in other organs such as the liver, kidneys and muscles due to the lack of adipose tissue, which leads to tissue damage.

Leptin also plays an important role in the immune system and sexual maturity. This can therefore lead to increased infections and disruptions in pubertal development and fertility. Particularly in patients with generalised lipodystrophy, leptin levels are very low, which leads to a particularly severe manifestation of secondary diseases and a considerable impairment of the quality of life of those affected.

There is currently no cure for lipodystrophy. Specialised nutritional therapy is essential for the treatment of the metabolic consequences. Patients with certain forms of lipodystrophy and low leptin levels may benefit from specialised therapy. Metreleptin, a recombinant human leptin analogue, is used as a leptin replacement therapy in combination with a diet to treat the consequences of leptin deficiency. The leptin supplied increases the breakdown of fat in the blood, muscles and liver and thus leads to a dramatic improvement in hypertriglyceridaemia, fatty liver, insulin resistance and diabetes mellitus. However, the lost subcutaneous fat tissue cannot be restored by leptin replacement therapy.

Other non-specific therapeutic approaches can also help to treat the secondary diseases of lipodystrophy (e.g. metformin for diabetes, statins or fibrates for hyperlipidaemia).