An inherited metabolic disorder mainly affecting young female adults characterized by
insulin resistance with glucose intolerance, hypertriglyceridemia, and partial lipodystrophy.
Slow onset initially
presenting with progressive loss of subcutaneous adipose tissue. Other features include
hypocomplementemia, glomerulonephritis, and autoimmune disorders.
Familial Partial Lipodystrophy (FPLD).
Familial Partial Lipodystrophy Type I (Köbberling Type): Characterized by loss of adipose tissue confined to the extremities, with
normal or increased amounts of fat on the face, neck, and trunk. So far, this type has been reported only in females.
Familial Partial Lipodystrophy Type II (Dunnigan Type; Familial Lipodystrophy of Limbs and Lower
Trunk; Reverse Partial Lipodystrophy; Lipoatrophic Diabetes): Characterized by partial lipodystrophy with
onset around puberty after a normal fat distribution in early childhood. The subcutaneous adipose tissue
gradually disappears from the upper and lower extremities and the gluteal and truncal regions. Clinical
features include a muscular appearance with prominent superficial veins, a double chin, fat neck, or
cushingoid appearance. Adipose tissue may accumulate in the axillae, back, labia majora, and
intraabdominal region. Acanthosis nigricans, hirsutism, and menstrual abnormalities (polycystic ovary syndrome) occur occasionally.
Affected patients are insulin resistant and may develop glucose intolerance and diabetes mellitus after
age 20 years.
Familial Partial Lipodystrophy Type III (Familial Partial Lipodystrophy Associated with PPARG Mutations): Characterized by frank type II diabetes requiring insulin treatment and
severe sustained hypertension.
Approximately 20 patients with FPLD I have been reported in the
literature. More than 200 cases of FPLD II have been described. Females are approximately
5 times more often affected than men. Both types, but particularly FPLD I, are most
likely far more common than previously thought.
All forms of FPLD (type I-III) are autosomal dominant
inherited, although for some cases of FPLD II X-linked dominant transmission has been
discussed. The genetic defects map to 1q21.2 and 3p25 for FPLD II,
to 7q11.23-q21 and 3p25 for FPLD III,
while for type I the
locus has not been determined, yet.
A missense mutation in the gene encoding lamins A and C
(LMNA). Lamins provide structural integrity of the nuclear envelope and are associated with
chromatins and other nuclear proteins. The exact mechanism by which lamins affect the fat
distribution remains to be elucidated.
Phenotype is characteristic, although it has been
confused with Cushing syndrome. MRI studies verify virtual absence of
subcutaneous fat in extremities with or without trunk involvement with excessive
collection of adipose tissue in the head and neck region.
Hypertriglyceridemia and hyperinsulinemia.
Type I is characterized by the gradual
disappearance of most subcutaneous adipose tissue from the lower extremities
and gluteal areas at puberty. Muscles and superficial veins become prominent
in these areas. In type II, there is also disappearance of adipose tissue
from the upper extremities and trunk, with simultaneous accumulation of
adipose tissue on the face and neck, giving a cushingoid appearance. Adipose
tissue may accumulate in ...