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The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 79086
A rare lipodystrophic syndrome characterized by loss of adipose tissue, and is a syndrome of insulin resistance that leads to increased cardiovascular risk. Acquired generalized lipodystrophy is related to a selective loss of subcutaneous adipose tissue occurring exclusively at the extremities (face, legs, arms, palms and sometimes soles).
More than 100 cases have been described and the female to male ratio is 3:1.
The clinical phenotype is similar to that of Berardinelli-Seip syndrome (see this term), but lipoatrophy appears secondarily during childhood, adolescence or adulthood, and as a result the syndrome is thought to be acquired. In some cases, loss of adipose tissue is localized, especially if it is preceded by a panniculitis. The syndrome is associated with a voracious appetite and an acceleration of growth in adolescents. One third of cases are accompanied by acanthosis nigricans and a polycystic ovary syndrome (see these terms). Hepatomegaly with steatosis and a risk of cirrhogenous progression is common. Biologically, hyperinsulinemia and insulin-resistant diabetes are observed, often associated with severe hypertriglyceridemia with low plasma levels of leptin and adiponectin. Proteinuria associated with focal segmental glomerulosclerosis or with membranoproliferative glomerulonephritis have been reported recently, as well as dysregulation of growth hormone. Three types of the disease have been described: 1) a form with panniculitis (inflammatory nodules followed by lipoatrophy), 2) an autoimmune form that is readily associated with other syndromes such as chronic active hepatitis, Hashimoto struma and hemolytic anemia, but also with dermatomyositis and Sjogren's syndrome (see these terms), 3) idiopathic.
The cause of the disease remains unknown. There may be infectious triggering factors (there was a recent case of the panniculitis type that appeared after tuberculosis) or an autoimmune mechanism. A recent publication showed activation of the classical complement pathway (low C4). This is in contrast to acquired partial lipodystrophy (see this term) which affects the upper half of the body and is characterized by an activation of the alternative complement pathway (low C3). Progression towards partial lipoatrophy, focal or generalized, has been reported in patients with dermatomyositis, amongst whom this could be a late relapse, and it is more common that the antibody anti-p155 is present. The hypothesis of an underlying genetic factor has not been rejected.
Diagnosis is clinical and should be confirmed by an assessment of body fat, in particular by biphotonic absorptiometry and magnetic resonance imaging.
Differential diagnoses include other forms of extreme insulin resistance (Rabson-Mendenhall syndrome, leprechaunism, Berardinelli type lipodystrophy and insulin resistance syndromes types A and B; see these terms) and other lipodystrophies.
Management and treatment
The treatment of the metabolic manifestations is a priori no different to the treatment of other forms of insulin resistance: physical exercise, insulin sensitizers such as metformin or pioglitazone, insulin (or preferably insulin analogues), antihypertensives, and monitoring and treatment of hypertriglyceridemia. The efficacy of recombinant human leptin has been demonstrated on the metabolic level but this therapy is not available in all countries. In serious autoimmune forms of the disease, immunosuppressive therapy may be indicated.
The prognosis is not well known but is probably related to cardiovascular risk (linked to the insulin-resistance syndrome) and to the underlying cause of the disease.
Visit the Orphanet disease page for more resources.
Source: GARD Last updated on 05-01-20
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