Several rare conditions are associated with loss of fatty tissue in a partial or generalized distribution.

Partial Lipodystrophy. Partial lipodystrophy may be familial or acquired. Loss of adipose tissue is not preceded by an inflammatory phase, and histopathologic examination reveals only absence of subcutaneous fat.

There are 3 forms of familial partial lipodystrophy (FPLD).

Type I (FPLD1-Kobberling) is characterized by loss of adipose tissue confined to the extremities and gluteal region. Fat distribution of the face, neck, and trunk may be normal or increased. Hyperlipidemia, insulin-resistant diabetes mellitus, and eruptive xanthomas may be seen. The gene is unknown, but only females are affected.
Type 2 (FPLD2-Dunnigan) is caused by mutations in the laminin A/C gene. Fat distribution is normal in childhood, but atrophy commences with puberty. Lipodystrophy is seen in the trunk, gluteal region, and extremities. Adipose tissue accumulates in the face and neck and may also be seen in the axillae, back, labia majora, and infra-abdominal region. Insulin-resistant diabetes mellitus and hypertriglyceridemia develop, but high-density lipoprotein and cholesterol levels are low. Both males and females are affected, but the diagnosis may be more difficult in males due to body habitus.
Type 3 (FPLD3) is caused by mutations in the peroxisome proliferation–activated receptor gamma (PPARG) gene. Lipodystrophy is seen in the limbs and gluteal region. Insulin-resistant diabetes mellitus, primary amenorrhea, acanthosis nigricans, hypertension, and fatty infiltration of the liver are present.

Acquired partial lipodystrophy (Barraquer-Simons syndrome) is rare. Females are more commonly affected. Fat loss begins in childhood or adolescence and affects the face, neck, arms, thorax, and upper abdomen. Excess fat is seen in the hips and legs, especially in females. Low levels of C3 are almost universally seen. C3 nephritic factor is also present. C3 nephritic factor stabilizes C3 convertase, allowing for unopposed activation of the alternate complement pathway and the decreased level of C3. Membranous proliferative glomerulonephritis and other autoimmune diseases may develop. Insulin-resistant diabetes mellitus is rare.

GENERALIZED LIPODYSTROPHY. Generalized lipodystrophy may also be congenital or acquired.

Congenital generalized lipodystrophy is seen in 2 forms.

Type 1 (Berardinelli-Seip congenital lipodystrophy type 1 [BSCL1]) is an autosomal recessive disorder caused by mutations in the 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT2) gene
Type 2 (Berardinelli-Seip congenital lipodystrophy type 2 [BSCL2]) is also autosomal recessive and caused by mutations in the seipin gene.

Marked lipodystrophy occurs at birth or in early infancy. Diabetes mellitus, hypertriglycidemia, hepatic steatosis, acanthosis nigricans, and muscular hypertrophy occur. BSCL2 is a more severe phenotype, with premature death occurring in ? 15%.

Acquired generalized lipodystrophy is also more common in females. Twenty-five per cent of patients present with an inflammatory panniculitis; 25% with an associated autoimmune disease, usually juvenile dermatomyositis; and the remaining half have neither. Fat loss begins in early childhood or adolescence and affects the majority of the body. Affected children are noted to have a voracious appetite. Acanthosis nigricans and hepatic steatosis develop in most patients, with 20% progressing to cirrhosis.

Localized lipoatrophy is an idiopathic condition that presents as annular atrophy at the ankles, a bandlike semicircular depression 2–4 cm in diameter on the thighs or, rarely, on the abdomen and upper groin as a centrifugally spreading, depressed, bluish plaque with an erythematous margin. It occurs predominantly in Japanese children.

Insulin lipoatrophy usually occurs ? 6 mo–2 yr after initiation of relatively high doses of insulin. A dimple or well-circumscribed depression at the site of injection is typically seen, although loss of fat may extend beyond the site of injection, leading to an extensive, depressed plaque. Biopsy reveals a marked decrease or absence of subcutaneous tissue, without inflammation or fibrosis. In some patients, hypertrophy occurs clinically. In these cases, the mid-dermal collagen is replaced by hypertrophic fat cells on histopathologic sections. The mechanism of insulin lipoatrophy may be cross reaction of insulin antibodies with fat cells; the incidence of this condition has decreased since the implementation of widespread use of highly purified insulins. Lesions may also be prevented by frequent alteration of injection sites.

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