ESPE Abstracts (2022) 95 P1-477

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

Homozygous LEPR mutation as a cause of early onset child hood obesity in a Pakistani girl

Muzna Arif , Fozia Memon , Khadija Humayun & Salman Kirmani

Aga Khan University, Karachi, Pakistan

Background: Monogenic nonsyndromic obesity is severe, has early-onset with abnormal eating behaviour and endocrine disorders. Leptin(LEP), Leptin receptor (LEPR), and Melanocortin 4 receptor (MC4R) gene mutations are identidied as the cause of early-onset childhood obesity. These pathogenic mutations are rare and have been described in less than 50 obese individuals worldwide, from consanguinous families.A cohort of Pakistani obese children from consanguineous parents showed LEP gene mutation in up to17% cases. LEP mutations result in a complete lack of its protein, loss of function mutations in the LEPR renders the carrier insensitive to leptin, both leptin and leptin receptor deficiency result in identical early-onset severe hyperphagic obesity. This is the first case of LEPR mutation leading to early onset obesity in a girl from our center.

Objective: To describe a case of morbid early onset childhood obesity due to LEPR and MC4R mutations.

Case summary: We report a 1 year old girl, weighing 23 KG(BMI:31.8kg/m2), with progressive and rapid weight gain since 1 month of life. Born at term with, no prenatal or postnatal concerns, parents were first cousins. Father, 2 paternal uncles and 5 maternal aunts had history of early onset obesity till 5-6 years of age after which their weights normalized. Her birth weight was 3 Kg,11.7 kg at 4 months of age(BMI:26.4kg/m2) and16 kg at 5 and a half months of age(BMI:30.4kg/m2) when she presented. She was on exclusive breast feeding. Weaning foods were very rarely taken. Her gross motor milestones were slightly delayed but intellectual development was normal with no other associated illness. Considering the possibility of a genetic form of obesity, a monogenic obesity panel was sent in which testing of 68 genes was done. Two homozygous Pathogenic variants were identified in LEPR,(Exon 4, c.133_136dup (P.Tyr46*).This sequence change creates loss of function in LEPR gene and leptin receptor deficiency with very early onset childhood obesity which is most likely the case in our patient giving the matching phenotype and clinical presentation. An additional heterozygous variant of uncertain significance identified in the MC4R gene,(Exon1, c.63_64del (P.Tyr21*)also creates a premature translational stop signal in the MC4R gene and is found in patients with early onset obesity. Parents genetic testing has been sent and is awaited.

Conclusions:Our case highlights the implication of rare LEPR mutations in severe early-onset obesity in a consanguineous family diagnosing which is important for understanding of satiety regulation. Genetic diagnosis can help devising strategies of lifestyle interventions to support the patient and parents in coping.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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