Monogenic leptin deficiency in early childhood obesity

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Early childhood obesity is a global health concern impacting children's physical and mental well-being.
• Identifying treatable causes like congenital leptin deficiency is crucial for effective management.
• Leptin deficiency is a significant, yet often overlooked, contributor to early-onset obesity.

Purpose of the Study:

• To diagnose monogenic leptin deficiency in Egyptian children with early-onset obesity (EOO).
• To investigate the prevalence and genetic basis of leptin deficiency in this cohort.
• To establish a diagnostic pathway for monogenic obesity in pediatric populations.

Main Methods:

• A cross-sectional study involving 80 Egyptian children with obesity onset within the first year of life (BMI > 2 SD).
• Comprehensive assessment including medical history, auxological measurements, serum leptin level analysis, and leptin gene sequencing.
• Utilized standard diagnostic criteria for early-onset obesity and genetic analysis techniques.

Main Results:

• Leptin deficiency was identified in 10 cases (12.5%) of early-onset obesity.
• Elevated leptin levels were observed in 18 cases (22.5%).
• Leptin gene variants were found in 30% of leptin-deficient children, including two novel homozygous pathogenic variants (c.104 T > G and c.34 delC) and one previously reported variant (c.313C > T).

Conclusions:

• Leptin deficiency represents a significant cause of monogenic obesity in Egyptian children experiencing early-onset obesity.
• Diagnosing leptin deficiency enables targeted therapeutic interventions, such as recombinant leptin therapy.
• Genetic analysis of the leptin gene is a valuable tool for identifying treatable causes of pediatric obesity.