BackgroundEarly childhood obesity poses a significant global public health challenge, necessitating the identification of treatable causes, particularly congenital leptin deficiencies. Serum leptin level measurement aids in diagnosing these rare contributors, guiding effective management. MethodsA Chinese family with early-onset obesity underwent LEP mutational screening via direct sequencing. mRNA expression and protein stability patterns of LEP were separately analyzed using qPCR and bioinformatics. ResultsWe present a case of a 12.5-year-old girl born to non-obese, non-consanguineous Chinese parents, exhibiting low leptin levels. Leptin gene sequencing revealed novel compound heterozygous mutations in exon 3. RT-PCR analysis showed the mutation didn't affect leptin production. Bioinformatics analysis indicated the variant rendered the leptin protein unstable. ConclusionLoss-of-function mutations in LEP underlies early-onset obesity in the patient.