Phenotypic expression of biomolecular abnormalities in the leptin gene: a case report

Siddiqa Soomauroo; Nesrine Dhieb; AbdelMuhaymen Missaoui; Yasmine Abdelkafi; Salah Dhoha Ben; Khouloud Boujelben; Faten Hadjkacem; Nadia Charfi; Mouna Mnif; Mongia Hachicha; Mouna Elleuch; Nabila Rekik

doi:10.1530/endoabs.110.EP867

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Endocrine Abstracts (2025) 110 EP867 | DOI: 10.1530/endoabs.110.EP867

ECEESPE2025 ePoster Presentations Metabolism, Nutrition and Obesity (164 abstracts)

Phenotypic expression of biomolecular abnormalities in the leptin gene: a case report

Siddiqa Soomauroo ¹ , Nesrine Dhieb ¹ , AbdelMuhaymen Missaoui ¹ , Yasmine Abdelkafi ¹ , Dhoha Ben Salah ¹ , Khouloud Boujelben ¹ , Faten Hadjkacem ¹ , Nadia Charfi ¹ , Mouna Mnif ¹ , Mongia Hachicha ² , Mouna Elleuch ¹ & Nabila Rekik ¹

Author affiliations

¹Hedi Chaker University Hospital, Department of Endocrinology, Sfax, Tunisia; ²Hedi Chaker University Hospital, Department of Paediatrics, Sfax, Tunisia

JOINT3923

Introduction: Over the past four decades, the prevalence of childhood obesity has increased drastically. Congenital leptin deficiency (CLD) is a very rare recessive genetic disorder caused by homozygous mutations in the LEP gene, leading to early-onset obesity. Children with CLD have a normal birth weight but rapidly gain weight within the first few months of life, resulting in severe hyperphagia and extreme obesity.

Objective: This study elucidates the phenotype associated with CLD through the report of an exceptional case involving a homozygous nonsense mutation in the exon of the leptin gene, of which only three other similar cases have been described.

Case Report: The patient, N.A., a 17-month-old girl, exhibited drastic weight gain from the age of 2 months, associated with an eating disorder characterized by severe hyperphagia. Her psychomotor development was normal, and she showed no signs of dysmorphic syndrome. The diagnosis was confirmed biologically by detecting a severely reduced circulating leptin level (< 1 ng/ml). Genetic analysis revealed a nucleotide change in exon 3 of the leptin gene, caused by a homozygous nonsense mutation in the LEP gene. Due to a lack of resources, our patient did not receive recombinant human leptin therapy. Managed solely with dietary and lifestyle interventions, her condition worsened, with an aggravation of the eating disorder, evolving into constant food-seeking behavior. By the age of 3 years and 7 months, she weighed 38 kg.

Conclusion: Given the genetic and therapeutic complexity of CLD cases, adaptations in healthcare pathways are necessary to alleviate both the socioeconomic burden of medical care and the financial strain on affected children and their families. To achieve this, frontline pediatricians must be trained and made aware of the importance of early detection of these rare cases. Additionally, significant efforts should be made to develop more accessible pharmacological leptin replacement therapy, ensuring that children in need can also benefit from treatment.