Congenital generalized lipodystrophy: The evaluation of clinical follow-up findings in a series of five patients with type 1 and two patients with type 4

• Published in: European journal of medical genetics 2020-04, Vol.63 (4), p.103819-103819, Article 103819
• Main Authors: Nilay Güneş, Kutlu, Tufan, Tekant, Gonca Topuzlu, Eroğlu, Ayşe Güler, Üstündağ, Nil Çomunoğlu, Öztürk, Birol, Onay, Hüseyin, Tüysüz, Beyhan
• Format: Article
• Language: English
• Subjects: Acyltransferases - genetics; Adolescent; Adult; AGPAT2 gene; Cardiomyopathy, Hypertrophic - etiology; Cardiomyopathy, Hypertrophic - genetics; CAVIN1 gene; Child; Child, Preschool; Congenital generalized lipodystrophy; Duodenal perforation; Duodenum - pathology; Fatty Liver - etiology; Fatty Liver - genetics; Female; Humans; Hyperinsulinism - etiology; Hyperinsulinism - genetics; Lipodystrophy, Congenital Generalized - complications; Lipodystrophy, Congenital Generalized - genetics; Male; Mutation; Pyloric stenosis; Pyloric Stenosis - etiology; Pyloric Stenosis - genetics; RNA-Binding Proteins - genetics; Young Adult
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2019.103819

Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by lipoatrophy affecting the face, limbs and trunk, acromegaloid features, hepatomegaly, hypertriglyceridemia, and insulin resistance. The aim of this study is to evaluate the long-term follow-up findings including gastrointestinal and cardiac manifestations of the patients with CGL1 and CGL4, caused by mutations in the AGPAT2 and CAVIN1 genes, respectively. Two patients aged 2 and 9 years with the same biallelic CAVIN1 mutation and five patients aged between 6 months and 11 years 4 months with AGPAT2 mutations have been followed up for 3–9 years. The patients were between 7 and 20 years of age at their last examination. One of the two patients with CGL4 had congenital pyloric stenosis. The other patient with CGL4 have developed recurrent duodenal perforations which have not been reported in CGL patients previously. The pathological examination of duodenal specimens revealed increased subserosal fibrous tissue and absent submucosal adipose tissue. None of the five CGL1 patients had gastrointestinal problems. Two patients with CGL4 developed hypertrophic cardiomyopathy (HCMP) and severe cardiac arrhythmia, only one patient with CGL1 had HCMP. Hyperinsulinemia was detected in one patient with CGL4 and three patients with CGL1, these three CGL1 patients also had acanthosis nigricans. Hepatic steatosis was detected in one patient with CGL4 and two patients with CGL1 by ultrasonography. In conclusion, these findings suggest that CGL4 patients should also be carefully followed up for gastrointestinal and cardiac manifestations.