Skip to main content
ENDO 2026 Main banner

Pediatric and Adolescent Endocrinology

ORF03-04 - Lipodystrophy Severity Score in Children: Disease Progression and Response to Leptin Replacement Theraphy in a Multi-Center Turkish Cohort

Saturday, June 13, 2026
10:00 AM - 10:15 AM CT
Location: Room W184ABC
Disclosure(s):
Samim Ozen, MD, PhD: No financial relationships to disclose
Elif A. Oral, MD: No relevant disclosure to display



Introduction:
Lipodystrophy is associated with a serious disease burden due to metabolic abnormalities and organ complications. Recently, a validated Lipodystrophy Severity Score (LDSS) became available to assess disease burden comprehensively. In this study, we aimed to evaluate disease progression and the impact of metreleptin treatment in patients with pediatric-onset lipodystrophy using the LDSS.
Materials and

Methods:
We conducted a retrospective medical chart review and calculated LDSS in a total of 422 visits from 73 patients (50 girls, 69%) diagnosed with pediatric-onset lipodystrophy at 26 academic centers throughout Türkiye. Of the 73 patients, 50 had congenital generalized lipodystrophy (CGL) (CGL1: 20, CGL2: 14, CGL3: 2, CGL4: 9, unclassified CGL: 9), 4 had acquired generalized lipodystrophy (AGL), 9 had familial partial lipodystrophy (FPLD) (FPLD2: 8, FPLD3: 1), 1 had acquired partial lipodystrophy (APL), 5 had progeroid lipodystrophy, and 4 had complex lipodystrophy syndromes.

Results:
The mean age at diagnosis was 8 ± 6 years and mean follow-up was 74 ± 59 months. Disease severity worsened significantly with age. Average LDSS increased from baseline 24 ± 21 to 32 ± 27 (p < 0.001) at the final leptin-naïve visit. Progression was evident even during early childhood but accelerated markedly during adolescence and young adulthood. A piecewise mixed linear model showed LDSS progression increased significantly after age 12 (by 1.606, p < 0.001). Disease progression was observed across all domains. During the first decade, lipid and liver domains were the main drivers of severity. Diabetes/insulin resistance became the predominant driver during the second decade, while cardiovascular, renal, and reproductive domains contributed significantly later. Microvascular complications of diabetes started emerging during late adolescence/young adulthood. Both generalized (GL) and partial (PL) forms showed significant progression; however, progression occurred earlier and was more severe in GL. Although the PL population size was limited, an increase in LDSS after the second decade of life was observed. Among CGL subtypes, CGL2 had the highest disease severity. Of the 73 patients, 22 (30%) received leptin replacement. While age was positively associated with LDSS, its effect decreased significantly after leptin replacement treatment (−0.507, p = 0.01). Using a piecewise linear mixed model with a knot at leptin initiation age, we compared LDSS change per unit age before and after treatment. LDSS decreased significantly after leptin replacement initiation (−4.5, p = 0.008).

Conclusion:
Disease severity in lipodystrophy progresses significantly from early childhood and accelerates during adolescence and young adulthood, affecting multiple domains. Leptin replacement therapy mitigates this progression and modifies the natural history of the disease.