ESPE Abstracts

Background: Congenital leptin deficiency is a rare cause of early-onset severe obesity. Clinical features of congenital leptin deficiency include early-onset severe obesity, marked hyperphagia, endocrine and metabolic alterations. Some patients have immune dysregulation.

Case report: We describe two siblings from Libya referred for severe obesity. A boy (patient 1) referred at the age of 4 years and 3 months and a girl (patient 2) at the age of 2 years and 3 months. The parents were consanguineous and normal weighted. Both children started developing severe obesity at the age of 6 months, associated with food seeking behaviour, recurrent respiratory infections, sleeping disorders, psychomotor delay. Weight of patient 1 was 45.7 kg (+5.2 SDS) and height 111 cm (+1.5 SDS). Weight of patient 2 was 25 kg (+ 4.9 SDS) and height was 90 cm (+ 0.4 SDS). At physical examination severe acanthosis nigricans and brachydactyly were present. Both children showed undetectable serum concentrations of leptin. Immunological investigations documented a significant reduction in transitional B Lymphocyte and a mild deficiency of CD16+CD56+ cells. Both patients had dyslipidemia and insulin resistance. Next generation sequencing revealed a frameshift novel variant in the leptin gene located in c.150_153delCAGT causing the introduction of the premature stop codon p.Val51ProfsTer19 at the protein level.

Conclusions: A novel mutation of leptin gene causing early onset severe obesity associated with metabolic alterations and immune dysfunction was identified. Early diagnosis leptin deficiency leads replacement therapy with recombinant human leptin (metreleptin) which modifies the natural history of this condition.