How to diagnose a lipodystrophy syndrome.

The spectrum of adipose tissue diseases ranges from obesity to lipodystrophy, and is accompanied by insulin resistance syndrome, which promotes the occurrence of type 2 diabetes, dyslipidemia and cardiovascular complications. Lipodystrophy refers to a group of rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as Dunnigan syndrome, which is a type of laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement. Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much more rare. The genetically determined generalized forms are also very rare and are linked to mutations of seipin AGPAT2, FBN1, which is accompanied by Marfan syndrome, or of BANF1, which is characterized by a progeroid syndrome without insulin resistance and with early bone complications. Glycosylation disorders are sometimes involved. Some genetically determined forms have recently been found to be due to autoinflammatory syndromes linked to a proteasome anomaly (PSMB8). They result in a lipodystrophy syndrome that occurs secondarily with fever, dermatosis and panniculitis. Then there are forms that are considered to be acquired. They may be iatrogenic (protease inhibitors in HIV patients, glucocorticosteroids, insulin, graft-versus-host disease, etc.), related to an immune system disease (sequelae of dermatopolymyositis, autoimmune polyendocrine syndromes, particularly associated with type 1 diabetes, Barraquer-Simons and Lawrence syndromes), which are promoted by anomalies of the complement system. Finally, lipomatosis is currently classified as a painful form (adiposis dolorosa or Dercum's disease) or benign symmetric multiple form, also known as Launois-Bensaude syndrome or Madelung's disease, which are sometimes related to mitochondrial DNA mutations, but are usually promoted by alcohol. In addition to the medical management of metabolic syndrome and the sometimes surgical treatment of lipodystrophy, recombinant leptin provides hope for genetically determined lipodystrophy syndromes, whereas modifications in antiretroviral treatment and tesamorelin, a GHRH analog, is effective in the metabolic syndrome of HIV patients. Other therapeutic options will undoubtedly be developed, dependent on pathophysiological advances, which today tend to classify genetically determined lipodystrophy as being related to laminopathy or to lipid droplet disorders.

Vantyghem MC ，Balavoine AS ，Douillard C ，Defrance F ，Dieudonne L ，Mouton F ，Lemaire C ，Bertrand-Escouflaire N ，Bourdelle-Hego MF ，Devemy F ，Evrard A ，Gheerbrand D ，Girardot C ，Gumuche S ，Hober C ，Topolinski H ，Lamblin B ，Mycinski B ，Ryndak A ，Karrouz W ，Duvivier E ，Merlen E ，Cortet C ，Weill J ，Lacroix D ，Wémeau JL ... -  《-》

[Primary lipodystrophies].

Capeau J ，Magré J ，Lascols O ，Caron M ，Béréziat V ，Vigouroux C ... -  《ANNALES D ENDOCRINOLOGIE》

Lipomatoses.

Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple, encapsulated or not, subcutaneous or sometimes visceral. In some cases, they form large areas of non-encapsulated fat hypertrophy, with a variable degree of fibrosis. They can develop despite the absence of obesity. They may be familial or acquired. At difference with lipodystrophy syndromes, they are not associated with lipoatrophy areas, except in some rare cases such as type 2 familial partial lipodystrophy syndromes (FPLD2). Their metabolic impact is variable in part depending on associated obesity. They may have functional or aesthetic consequences. Lipomatosis may be isolated, be part of a syndrome, or may be visceral. Isolated lipomatoses include multiple symmetrical lipomatosis (Madelung disease or Launois-Bensaude syndrome), familial multiple lipomatosis, the painful Dercum's disease also called Adiposis Dolorosa or Ander syndrome, mesosomatic lipomatosis also called Roch-Leri lipomatosis, familial angiolipomatosis, lipedema and hibernomas. Syndromic lipomatoses include PIK3CA-related disorders, Cowden/PTEN hamartomas-tumor syndrome, some lipodystrophy syndromes, and mitochondrial diseases, especially MERRF, multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson disease, Pai or Haberland syndromes. Finally, visceral lipomatoses have been reported in numerous organs and sites: pancreatic, adrenal, abdominal, epidural, mediastinal, epicardial… The aim of this review is to present the main types of lipomatosis and their physiopathological component, when it is known.

Dupuis H ，Lemaitre M ，Jannin A ，Douillard C ，Espiard S ，Vantyghem MC ... -  《-》

[Lipodystrophic syndromes: congenital or acquired diseases of adipose tissue].

Capeau J ，Vigouroux C ，Magré J ，Lascols O ，Caron M ，Bastard JP ... -  《COMPTES RENDUS BIOLOGIES》

[Lipodystrophies].

Human lipodystrophies represent a group of diseases characterized by altered body fat amount and/or repartition. Most forms of lipodystrophies are associated with metabolic alterations such as insulin resistance, diabetes and dyslipemia, leading to diabetic complications, increased cardiovascular risk or liver steatosis. Lipodystrophies can be classified as genetic or acquired, generalized or partial. Genetic forms such as Berardinelli-Seip syndrome or partial familial lipodystrophies are uncommon and acquired forms are much more frequent. Beside the rare Lawrence or Barraquer-Simons syndromes, the main forms of acquired lipodystrophies are those observed in HIV-infected people treated with antiretroviral therapies or in people exposed to an endogenous or an exogenous hypercortisolism. The treatment of lipodystrophies is difficult. Lifestyle modifications (e.g., specific diet, physical training) may be helpful but are usually insufficient. Associated metabolic disorders should be treated as soon as possible with insulin sensitizers, insulin and lipid lowering drugs. New therapies such as leptin have been proven to be helpful in some genetic or acquired forms of lipodystrophy.

Fardet L ，Vigouroux C ，Capeau J 《-》