TY - JOUR
T1 - Metabolic and other morbid complications in congenital generalized lipodystrophy type 4
AU - Akinci, Gulcin
AU - Alyaarubi, Saif
AU - Patni, Nivedita
AU - Alhashmi, Nadia
AU - Al-Shidhani, Azza
AU - Prodam, Flavia
AU - Gagne, Nancy
AU - Babalola, Funmbi
AU - Al Senani, Aisha
AU - Muniraj, Kavitha
AU - Elsayed, Solaf M.
AU - Beghini, Marianna
AU - Saydam, Basak Ozgen
AU - Allawati, Moosa
AU - Vaishnav, Madhumati S.
AU - Can, Ender
AU - Simsir, Ilgin Y.
AU - Sorkina, Ekaterina
AU - Dursun, Fatma
AU - Kamrath, Clemens
AU - Cavdar, Umit
AU - Chakraborty, Partha P.
AU - Dogan, Ozlem Akgun
AU - Al Hosin, Aliya
AU - Al Maimani, Ashwaq
AU - Comunoglu, Nil
AU - Hamed, Ahmed
AU - Huseinbegovic, Tea
AU - Scherer, Thomas
AU - Curtis, Jacqueline
AU - Brown, Rebecca J.
AU - Topaloglu, Haluk
AU - Simha, Vinaya
AU - Wabitsch, Martin
AU - Tuysuz, Beyhan
AU - Oral, Elif A.
AU - Akinci, Baris
AU - Garg, Abhimanyu
N1 - Publisher Copyright:
© 2024 Wiley Periodicals LLC.
PY - 2024/1/17
Y1 - 2024/1/17
N2 - Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346–3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.
AB - Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346–3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.
KW - CAVIN1
KW - congenital generalized lipodystrophy
KW - gastrointestinal disease
KW - metabolic abnormalities
KW - myopathy
KW - ventricular tachycardia
UR - http://www.scopus.com/inward/record.url?scp=85182455734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85182455734&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e95da984-1279-39ec-98c0-eca98c525e7b/
U2 - 10.1002/ajmg.a.63533
DO - 10.1002/ajmg.a.63533
M3 - Article
C2 - 38234231
AN - SCOPUS:85182455734
SN - 1552-4825
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
ER -