Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive syndrome characterized by extreme paucity of adipose tissue since birth, acanthosis nigricans, severe insulin resistance, marked hypertriglyceridemia, and early-onset diabetes mellitus. Recently, we reported mutations in the 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) gene in CGL pedigrees linked to chromosome 9q34 (CGL1 subtype), and mutations in the Seipin gene were reported in pedigrees linked to chromosome 11q13 (CGL2 subtype). Whether the two subtypes have differences in body fat distribution has not been investigated. We, therefore, compared whole-body adipose tissue distribution by magnetic resonance imaging in 10 CGL patients, of whom seven (six females, one male) had CGL1 and three (two males, one female) had CGL2. Both subtypes had marked lack of metabolically active adipose tissue located at most sc, intermuscular, bone marrow, intraabdominal, and intrathoracic regions. Paucity of mechanical adipose tissue in the palms, soles, orbits, scalp, and periarticular regions was noted in CGL2, whereas it was well preserved in CGL1 patients. We conclude that CGL patients with Seipin mutations have a more severe lack of body fat, which affects both metabolically active and mechanical adipose tissue, compared with patients with mutations in the AGPAT2 gene.