Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey.
CONTEXT Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near total lack of body fat. OBJECTIVE We aimed to study natural history and disease burden of various subtypes of CGL. DESIGN We attempted to ascertain nearly all patients with CGL in Turkey. SETTING This was a nationwide study. PATIENTS OR OTHER PARTICIPANTS Participants included 33 patients (22 families) with CGL and 30 healthy controls. MAIN OUTCOME MEASURE(S) We wanted to ascertain genotypes by sequencing of the known genes. Whole body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end organ complications were measured on prospective follow up. RESULTS Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316+1G>T) Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease causing mutations (CGL2) including four novel mutations (c.280C>T, c.631delG, c.62A>T, and c.465 468delGACT) Two homozygous PTRF mutations (c.481 482insGTGA and c.259C>T) were identified (CGL4) Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events. CONCLUSIONS CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end organ complications in patients with CGL.
The Journal of clinical endocrinology and metabolism