TY - JOUR
T1 - Natural history of congenital generalized lipodystrophy
T2 - A nationwide study from Turkey
AU - Akinci, Baris
AU - Onay, Huseyin
AU - Demir, Tevfik
AU - Ozen, Samim
AU - Kayserili, Hulya
AU - Akinci, Gulcin
AU - Nur, Banu
AU - Tuysuz, Beyhan
AU - Ozbek, Mehmet Nuri
AU - Gungor, Adem
AU - Simsir, Ilgin Yildirim
AU - Altay, Canan
AU - Demir, Leyla
AU - Simsek, Enver
AU - Atmaca, Murat
AU - Topaloglu, Haluk
AU - Bilen, Habib
AU - Atmaca, Hulusi
AU - Atik, Tahir
AU - Cavdar, Umit
AU - Altunoglu, Umut
AU - Aslanger, Ayca
AU - Mihci, Ercan
AU - Secil, Mustafa
AU - Saygili, Fusun
AU - Comlekci, Abdurrahman
AU - Garg, Abhimanyu
N1 - Publisher Copyright:
© 2016 by the Endocrine Society.
PY - 2016/7
Y1 - 2016/7
N2 - 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).Twohomozygous PTRFmutations(c.481-482insGTGAandc.259C-T)wereidentified (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.
AB - 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).Twohomozygous PTRFmutations(c.481-482insGTGAandc.259C-T)wereidentified (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.
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U2 - 10.1210/jc.2016-1005
DO - 10.1210/jc.2016-1005
M3 - Article
C2 - 27144933
AN - SCOPUS:84978382674
SN - 0021-972X
VL - 101
SP - 2759
EP - 2767
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 7
ER -