Acquired generalized lipodystrophy

Alternate names

Lawrence syndrome; Lawrence-Seip syndrome; Acquired lipoatrophic diabetes

Definition

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).

Epidemiology

More than 100 cases have been described and the female to male ratio is 3:1.

Cause

• 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 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.

Signs and symptoms

• The clinical phenotype is similar to that of Berardinelli-Seip syndrome , 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 .
• 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 , 3) idiopathic.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 100% of people have these symptoms

• Generalized lipodystrophy

80%-99% of people have these symptoms

• Hyperinsulinemia

30%-79% of people have these symptoms

• Autoimmunity(Autoimmune disease)
• Calf muscle pseudohypertrophy
• Cardiomyopathy(Disease of the heart muscle)
• Hepatic steatosis(Fatty infiltration of liver)
• Insulin-resistant diabetes mellitus(Insulin resistant diabetes)
• Progeroid facial appearance(Premature aged appearance)

5%-29% of people have these symptoms

• Abnormality of complement system
• Acanthosis nigricans(Darkened and thickened skin)
• Accelerated skeletal maturation(Advanced bone age)
• Acute pancreatitis(Acute pancreatic inflammation)
• Cirrhosis(Scar tissue replaces healthy tissue in the liver)
• Generalized hirsutism(Excessive hairiness over body)
• Generalized hyperpigmentation
• Hepatomegaly(Enlarged liver)
• Hypertension
• Hypertriglyceridemia(Increased plasma triglycerides)
• Myopathy(Muscle tissue disease)
• Panniculitis(Inflammation of fat tissue)
• Polycystic ovaries
• Proteinuria(High urine protein levels)

1%-4% of people have these symptoms

• Astrocytoma
• Lymphoma(Cancer of lymphatic system)
• Unicameral bone cyst

Diagnosis

Diagnosis is clinical and should be confirmed by an assessment of body fat, in particular by biphotonic absorptiometry and magnetic resonance imaging.

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.

Prognosis

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.

NIH genetic and rare disease info

• NIH info on Acquired generalized lipodystrophy

Acquired generalized lipodystrophy is a rare disease.

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