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Congenital generalised lipodystrophy

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Lipodystrophies (1,2,3)

  • a group of heterogeneous disorders characterized by varying degrees of body fat loss and predisposition to insulin resistance and its metabolic complications
  • subclassified depending on the degree of fat loss and whether the disorder is genetic or acquired
  • two most common genetic varieties include congenital generalized lipodystrophy and familial partial lipodystrophy
  • without sufficient adipose tissue there is disruption of the body's system for regulating energy use and storage
  • results in lipid accumulation in abnormal sites such as the liver and muscle
  • metabolic abnormalities often occur with lipodystrophy, including: insulin resistance with resultant hyperinsulinemia and diabetes; hepatic steatosis or steatohepatitis; and dyslipidaemia with severe hypertriglyceridaemia
  • associated lack of leptin, particularly in people with generalised lipodystrophy, leads to symptoms such as hyperphagia. It may also contribute to the metabolic abnormalities
  • hyperphagia, muscle pain and female reproductive dysfunction also have a significant effect on quality of life. Lipodystrophy is often diagnosed late in the disease course or remains undiagnosed

prevalence of lipodystrophy depends on the subtype

  • is around 2.5 per 1 million of the population overall, with partial lipodystrophy being slightly more common. It is estimated that there are around 200 people with lipodystrophy in England; a proportion of these people will be eligible for metreleptin treatment (3)

Congenital Generalized Lipodystrophy

  • congenital generalized lipodystrophy, sometimes referred to as Berardinelli-Seip syndrome, is an uncommon lipodystrophy variant with significant and sometimes near-total fat loss
  • chacterized by a near absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biologic features include:
    • acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia.
    • studies of pituitary and adrenal function including growth hormone assays have been normal. Polycystic ovaries, muscular hypertrophy, and mental retardation have occurred in some cases

Familial Partial Lipodystrophy

  • Familial partial lipodystrophy is most often an autosomal dominant condition with fat loss primarily involving the extremities, more commonly lower than upper.

Acquired Generalized Lipodystrophy

  • acquired generalized lipodystrophy is an extremely rare condition of widespread subcutaneous fat loss.

Acquired Partial Lipodystrophy

  • acquired partial lipodystrophy, or Barraquer-Simons syndrome, is characterized by gradual loss of fat from the upper body and truncal region during childhood. Over the past few decades, however, highly active anti-retroviral therapy induced lipodystrophy has become the most common form of acquired partial lipodystrophy


  • management of lipodystrophies is dependent upon the specific subtype and the extent of associated metabolic abnormalities
  • for patients with severe metabolic derangement, it is important to implement the use of lipid-lowering agents and diabetic medications
  • with a goal of increasing insulin sensitivity, pioglitazone has been shown to be more efficacious than metformin in this patient population
    • severe cases may require insulin
  • leptin analogs, particularly metreleptin, have shown efficacy in maintaining normal metabolism in patients who cannot effectively synthesize leptin naturally
    • Metreleptin is recombinant human leptin
    • NICE state (3):
      • Metreleptin is recommended, within its marketing authorisation, as an option for treating the complications of leptin deficiency in lipodystrophy for people who are 2years and over and have generalised lipodystrophy
      • Metreleptin is recommended as an option for treating the complications of leptin deficiency in lipodystrophy for people who are 12years and over, have partial lipodystrophy, and do not have adequate metabolic control despite having standard treatments. It is only recommended if they have an HbA1c level above 7.5%, or fasting triglycerides above 5.0mmol/litre, or both.


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