A cohort analysis of familial partial lipodystrophy from two Mediterranean countries

• Published in: Diabetes, obesity & metabolism Vol. 26; no. 11; pp. 4875 - 4886
• Main Authors: Fernández‐Pombo, Antía, Yildirim Simsir, Ilgin, Sánchez‐Iglesias, Sofía, Ozen, Samim, Castro, Ana I., Atik, Tahir, Loidi, Lourdes, Onay, Huseyin, Prado‐Moraña, Teresa, Adiyaman, Cem, Díaz‐López, Everardo Josué, Altay, Canan, Ginzo‐Villamayor, Maria José, Akinci, Baris, Araújo‐Vilar, David
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2024; Wiley Subscription Services, Inc
• Subjects: Adult; Age; Body mass index; Cardiovascular disease; Cohort Studies; Coronary artery disease; Coronary vessels; Diabetes mellitus; Diagnosis; familial partial lipodystrophy; Fatty liver; Female; Genotypes; Heart diseases; Humans; hypertriglyceridaemia; Hypertriglyceridemia - complications; Hypertriglyceridemia - epidemiology; Lamin Type A - genetics; Lipodystrophy; Lipodystrophy, Familial Partial - complications; Lipodystrophy, Familial Partial - epidemiology; Lipodystrophy, Familial Partial - genetics; Liver diseases; LMNA; Longitudinal Studies; Male; metabolic abnormalities; Metabolism; Middle Aged; Myocardial infarction; Phenotypes; PPARG; Retinopathy; Spain - epidemiology; Steatosis; Turkey - epidemiology; Vein & artery diseases; Turkey; Spain; Mediterranean Area; metabolic abnormalities; familial partial lipodystrophy; PPARG; diabetes mellitus; hypertriglyceridaemia; LMNA
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.15882

Aim
To assess the disease burden of familial partial lipodystrophy (FPLD) caused by LMNA (FPLD2) and PPARG (FPLD3) variants to augment the knowledge of these rare disorders characterized by selective fat loss and metabolic complications.
Materials and Methods
An observational longitudinal study, including 157 patients (FPLD2: 139 patients, mean age 46 ± 17 years, 70% women; FPLD3: 18 patients, mean age: 44 ± 17 years, 78% women) from 66 independent families in two countries (83 from Turkey and 74 from Spain), was conducted.
Results
Patients were diagnosed at a mean age of 39 ± 19 years, 20 ± 16 years after the first clinical signs appeared. Men reported symptoms later than women. Symptom onset was earlier in FPLD2. Fat loss was less prominent in FPLD3. In total, 92 subjects (59%) had diabetes (age at diagnosis: 34 ± 1 years). Retinopathy was more commonly detected in FPLD3 (P < .05). Severe hypertriglyceridaemia was more frequent among patients with FPLD3 (44% vs. 17%, P = .01). Hepatic steatosis was detected in 100 subjects (66%) (age at diagnosis: 36 ± 2 years). Coronary artery disease developed in 26 patients (17%) and 17 (11%) suffered from a myocardial infarction. Turkish patients had a lower body mass index, a higher prevalence of hepatic steatosis, greater triglyceride levels and a tendency towards a higher prevalence of coronary artery disease. A total of 17 patients died, with a mean time to death of 75 ± 3 years, which was shorter in the Turkish cohort (68 ± 2 vs. 83 ± 4 years, P = .01). Cardiovascular events were a major cause of death.
Conclusions
Our analysis highlights severe organ complications in patients with FPLD, showing differences between genotypes and Mediterranean countries. FPLD3 presents a milder phenotype than FPLD2, but with comparable or even greater severity of metabolic disturbances.