ESPE Abstracts

Introduction: Monogenic obesity is a rare form of obesity. It should be suspected if patients have severe early-onset obesity, rapid weight gain in the first 2 years of life, hyperphagia, positive family history, and additional clinical manifestations. Genetic testing is highly recommended in such cases, as new pharmacological therapies for several types of genetic obesity exist. Hence, we sought to evaluate the clinical, laboratory and molecular characteristics of patients with early-onset obesity attending Alexandria University Children's Hospital, Egypt.

Methods: This study was conducted on 28 children with early-onset obesity (onset <5 years of age) with BMI Z-score >2SD according to WHO growth charts. Approval of Alexandria University Ethical Committee, and an informed consent from parents were obtained. Detailed history taking, and physical examination were done. Routine laboratory investigations, lipid profile, thyroid function tests were performed. Additionally, glucose homeostasis and serum leptin were assessed.

Results: The majority of patients were males (67.86%). Age of onset of obesity ranged from 2-48 months, with a mean of 11.07±12.79 months. Hyperphagia was a predominant feature in 100% of patients. Fifteen patients (53.57%) had consanguineous parents. Most of the patients had family members with obesity (75%), while only 42.76% had family history of early-onset obesity. Almost 46% of patients had developmental delay. Seven percent of patients had stage 2 hypertension. Two patients (7.14%) were short, while 5 (17.86%) had tall stature. Fifteen patients (53.57%) had associated clinical features including eye abnormalities, dysmorphic features, neurological manifestations, polydactyly, skeletal abnormalities, and hepatomegaly. Almost 31% of males had micropenis. Seven patients (25%) were suspected to have syndromic obesity. Nine patients (32.14%) had insulin resistance, and 17.85% had prediabetes. Three patients (10.71%) had hypercholesterolemia and 50% had hypertriglyceridemia. One patient (3.57%) had hypopituitarism. Serum leptin was high in majority of patients. Only one patient had very low serum leptin (0.47 ng/dl), and was suspected to have congenital leptin deficiency. Serum leptin was significantly higher in females than males (P = 0.042^*). There was also a significant positive correlation between serum leptin and BMI Z-score, and serum TG (P = 0.044^*, P = 0.025^* respectively). WES was done to 15 patients, and 3 genetic mutations were identified: LEPR, MC4R, and GNAS gene mutations.

Conclusion: Early identification of genetic causes of obesity is important. Therefore, it is essential to have a high index of suspicion, especially in those with early-onset obesity, consanguinity, or those with associated clinical features, as molecular testing may not always be available.