(C-197) Prevalence of congenital and acquired generalized lipodystrophy in the EU

Background: Generalized lipodystrophy (GLD), encompassing both congenital and acquired, is a serious, ultra-rare disease characterized by near-total loss of subcutaneous tissue in the absence of a catabolic state or nutritional deprivation. GLD prevalence was estimated to be 0.96 cases per 1,000,000 in the European Union (EU) but the estimate included studies from literature search conducted through May 2012 and the prevalence of congenital and acquired GLD has not be estimated.

Objectives: To estimate the prevalence of GLD and its two subtypes ─ congenital and acquired ─ in the EU population.

Methods: An extensive literature search of GLD cases reported in literature published between January 1, 2000 and August 31, 2024 among 30 European Economic Area (EEA) countries including EU27, Iceland, Liechtenstein, and Norway was conducted. Searches were conducted in PubMed, Embase, and Google Scholar using disease-specific terms such as "lipodystrophy,” “Berardinelli-Seip syndrome,” and "Lawrence-Seip syndrome," along with “prevalence,” and “incidence.” Additional references were identified using snowballing technique. Publications were excluded if they were: 1) published before 2000; 2) conducted in countries outside of the EEA; 3) reviews that discussed LD but did not report number of cases; 4) reported number of LD cases, but did not specify number of GLD cases; or 5) about disease mechanism or treatment. Deduplication was conducted by keeping unique cases if cases were reported in more than one study, and deceased cases were removed based on data reported in the publications. To estimate prevalence, cases of congenital, acquired, and total GLD were summed and the denominator was derived as population size in 30 EEA countries in 2023.

Results: Among 907 identified articles (367 from PubMed and 540 from Embase), 72 papers were reviewed, and an additional 4 papers were included following the Google Scholar search and snowballing. Among 76 papers a total of 464 cases of GLD were identified. After deduplication and removing deceased cases, 333 unique cases of GLD [80.8%(n=269) congenital, 16.8%(n=56) acquired, and 2.4%(n=8) with congenital/acquired unknown] were identified across 65 publications. Among them, 87.7% of publications (n=57) are case report/series. With an EU population size of 454,957,630, the prevalence of congenital, acquired, and overall GLD was estimated to be 0.59, 0.12, and 0.73 per 1,000,000, respectively.

Conclusions: GLD prevalence in the EU is estimated to be < 1 per 1,000,000, of which congenital GLD accounts for approximately 80% of the cases. The prevalence could be underestimated due to underdiagnosis and underreporting.