ESPE2023 Poster Category 1 Fat, Metabolism and Obesity (97 abstracts)
Leptin receptor’s mutation in a patient with childhood obesity and hyperphagia
Cristina Partenope 1 , Elena Dondi 2 , Irene De Marchi 2 , Valentina Antoniotti 1 , Giorgia Monteleone 1 , Carlo Bianco 1 , Ilaria Montafia 1 , Federica Pagliero 1 , Giulia Aquisti 1 , Antonella Petri 1 , Ivana Rabbone 1 , Flavia Prodam 3 & Simonetta Bellone 1
1SCDU of Pediatrics, Department of Health Science, University of Piemonte Orientale, Novara, Italy. 2Department of Pediatrics, S. Andrea Hospital, Vercelli, Italy. 3SCDU of Endocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
Introduction: Genetic factors play an important role in determining individual susceptibility to weight gain and obesity. In the last few years, several genetic variants have been identified as monogenic forms of obesity. Among them, Leptin (LEP) and its receptor on hypothalamic neurons (LEPR) are key players in the regulation of body weight, food intake and energy homeostasis. Pathogenic variants in the LEPR gene cause severe childhood-onset obesity with an autosomal recessive inheritance.
Case Presentation: N.Y, male, aged 1.73 years, was referred to our Centre for excessive weight and hyperphagia. He was born at full term from Egyptian non consanguineous parents. Birth weight was 3920 g, length 53 cm and head circumference 34.5 cm (adequate for gestational age). He was breastfed for 15 months and he was regularly weaned at 6 months. He had normal psychomotor development. He had a significant weight gain within the first months of life (+ 1 kg per month). His diet was varied but with many snacks between meals. He ate every couple of hours. At 1.73 years old his length was 84.4 cm (-0.19 SDS), his weight 21 kg (+5.4 SDS), his BMI 29.48 kg/m2 (+6.59 SDS) and his head circumference 49.5 cm. Blood tests showed microcytic, hypochromic anemia, hypovitaminosis D and hypertriglyceridemia. Liver and renal function, thyroid function tests and adrenal function were within normal limits. At examination, adipomastia and acanthosis were detected. Considering the clinical picture, we performed NGS genetic test. Two variants of unknown clinical significance (VUS) c.3G>A p.Met1? and c.1345T>G p.(Trp449Gly) were detected, both in heterozigosity in the LEPR gene. Additionally, the variant of unknown significance c.661A>G p.(Asn221Asp) was detected in heterozygosity in the PCSK1 gene. The c.1345T>G p.(Trp449Gly) variant of the LEPR gene has not been described previously. The bioinformatic analysis predicts it to have a deleterious effect. Therefore, this should be classified as a VUS, suspected to be pathogenic. The variant in PCSK1 gene is described in the literature as a polygenic risk variant for obesity. Finally, we tested the patient’s parents. Father carried the c.1345T>G p.(Trp449Gly) variant, whereas mother carried the c.3G>T p.Met1? variant. Clinical and endocrinological follow-up of the patient is still ongoing.
Conclusion: The presence of monogenic mutations should be suspected in children with early onset obesity and hyperphagia. It is crucial to recognize pediatric obese patients to set a specific diagnostic path and management.
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