ESPE Abstracts (2022) 95 P1-65

ESPE2022 Poster Category 1 Fat, Metabolism and Obesity (73 abstracts)

Congenital Leptin Receptor deficiency: An Indian family with novel Homozygous LEPR gene mutation (LEPR):c.1752G>A (P.Lys584=) presenting with severe early onset obesity

Prashant Patil 1 , Dr Sakina Rajgara 2 & Dr Vidya Thakur 2


1NH SRCC Children's hospital, Mumbai, India; 2Seth VC vora Rajawadi Hospital, Mumbai, India

Introduction: Congenital deficiency of the leptin receptor is an extremely rare cause of early-onset monogenic obesity with rapid weight gain and compulsive overeating. LEPR mutations is responsible for extreme form of obesity associated with other endocrine abnormalities and respiratory tract infection. Till date, approximately 50 families have been reported to have mutations in the leptin receptor gene.

Case: 9-year-old girl and her 15-month-old brother born of third-degree consanguineous marriage with Asian ethnicity came for obesity assessment. Their elder sibling with morbid obesity succumbed at 1.5 years. Both children had normal birth weight with rapid weight gain during early infancy. Girl started to put on weight after 3 months of age (weight 10.3 kg; Z score -4.77) rapidly increasing to 19 kg (Z score -6.66) at 11 months. She had undergone bariatric surgery twice first at 11 months of age and later at 7years due to rapid weight gain [weight-49 kg and Z score -3.02] and type 2 DM. Boy also started to put on weight after 4 months with current weight of 18 kgs (Z score: 5.78) and length 80 cm s (Z score –0.77) with weight for height more than 99th percentile (Z score -6.82). Both had dyslipidaemia and high serum leptin levels. WES reported novel homozygous mutation synonymous variant NM_002303.6 (LEPR):c.1752G>A (P.Lys584=) on chromosome 1p31, which had not been reported previously. The nucleotide c.1752 in LEPR is predicted conserved by GERP++ and PhyloP across 100 vertebrates. The variant is segregating in two affected siblings whose serum leptin levels were also elevated, parents and an unaffected sibling were heterozygous carriers, whereas another unaffected sibling does not harbour the variant. For these reasons, this variant was classified as Pathogenic variant in our case. This is only second family in India with LEPR gene mutation and first with novel mutation. Setmelanotide is a selective melanocortin-4 receptor agonist which has been approved by US FDA in November 2020 for genetically proven obesity with LEPR mutation in children older than 6 years. Currently Setmelanotide is not available in India but could be used in future.

Conclusion: Our case illustrates the importance of early molecular genetic diagnostics in patients with severe, early-onset obesity to avoid lengthy diagnostic and unsuccessful and frustrating therapeutic procedures especially where consanguinity is more common. Improving overall awareness and availability of genetic testing will help these patients with monogenic obesity to gain access to treatment with recently developed newer drugs.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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