Natural history of congenital generalized lipodystrophy: A nationwide study from Turkey

Baris Akinci, Huseyin Onay, Tevfik Demir, Samim Ozen, Hulya Kayserili, Gulcin Akinci, Banu Nur, Beyhan Tuysuz, Mehmet Nuri Ozbek, Adem Gungor, Ilgin Yildirim Simsir, Canan Altay, Leyla Demir, Enver Simsek, Murat Atmaca, Haluk Topaloglu, Habib Bilen, Hulusi Atmaca, Tahir Atik, Umit CavdarUmut Altunoglu, Ayca Aslanger, Ercan Mihci, Mustafa Secil, Fusun Saygili, Abdurrahman Comlekci, Abhimanyu Garg

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2759-2767
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number7
StatePublished - Jul 2016

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Natural history of congenital generalized lipodystrophy: A nationwide study from Turkey'. Together they form a unique fingerprint.

Cite this