Citations 2
Lipodystrophy Severity Score to Assess Disease Burden in Lipodystrophy
Brown, Rebecca J. , Akıncı, Barış , Yosef, Matheos , Phillips, Helen , Khalatbari, Shokoufeh , Santini, Ferruccio , Brush, Maiah, Meral, Rasimcan , Prodam, Flavia , Schnurbein, Julia von , Sorice, Gian Pio , Güler, Merve Çelik , Patni, Nivedita , Tanrıkulu, Seher , Ozgen, Basak S, Foss‐Freitas, Maria Cristina , Özışık, Seçil , Segrestin, Bérénice , Özcan, Büşra, Adıyaman, Süleyman Cem , Musolino, Gianluca , Sekizkardes, Hilal , Musso, Carla , Simha, Vinaya , Stears, Anna, Gambineri, Alessandra , Semple, Robert K. , Prodam, Flavia , von Schnurbein, Julia , Sekizkardes, Hilal , Lebenthal, Yael , Simha, Vinaya , Wabitsch, Martin , Oral, Elif A , Brown, Rebecca J. , Sorkina, Ekaterina , Vigouroux, Corinne , Ceccarini, Giovanni , Zeybel, Müjdat , Al-Yaarubi, Saif , Ozgen, Basak S, Özen, Samim , Şimşir, İlgın Yıldırım , Scherer, Thomas , Lima, Josivan Gomes , Araújo‐Vilar, David , Hegele, Robert Alexander , Oral, Elif A
The Journal of Clinical Endocrinology & Metabolism | February 19, 2025 | Volume: 110 | Issue: 11 | Pages: 3243-3255
Abstract Context Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities. Objective Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact. Design An 8-domain LDS was developed by 8 disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to the Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at 2 different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in 2 cohorts of patients with lipodystrophy treated with metreleptin. Results LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by 1 or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility and high reliability by intraclass correlation coefficients (>0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R = 0.79-0.99, P < .001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P < .001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P = .04). Conclusion The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.
Metabolic and other morbid complications in congenital generalized lipodystrophy type 4
Akıncı, Gülçin , Patni, Nivedita , Alhashmi, Nadia, Al‐Shidhani, Azza, Prodam, Flavia , Gagné, Nancy , Babalola, Funmbi , Senani, Aisha Al , Muniraj, Kavitha , Beghini, Marianna , Saydam, Başak Özgen , Allawati, Moosa , Vaishnav, Madhumati S. , Can, Ender, Kamrath, Clemens , Çavdar, Ümit , Hosin, Aliya Al, Maimani, Ashwaq Al, Hamed, Ahmed, Huseinbegovic, Tea, Scherer, Thomas , Curtis, J. E., Brown, Rebecca J. , Topaloğlu, Haluk , Simha, Vinaya , Akıncı, Barış , Garg, Abhimanyu , Akinci, Baris , Garg, Abhimanyu , Prodam, Flavia , Al-Yaarubi, Saif , Elsayed, Solaf Mohamed , Şimşir, İlgın Yıldırım , Sorkina, Ekaterina , Dursun, Fatma , Chakraborty, Partha Pratim , Doğan, Özlem Akgün , Çomunoğlu, Nil , Hamed, Ahmed, Curtis, Jacqueline, Brown, Rebecca J. , Wabitsch, Martin , Tüysüz, Beyhan , Oral, Elif A
American Journal of Medical Genetics Part A | January 18, 2024 | Volume: 194 | Issue: 6 | Pages: No page available
AbstractMorbidity 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.