IMPE Abstracts

Monogenic obesity is a rare, severe condition, associated with early-onset weight gain. In the last years, due to advances in genetic technique and sequencing technology, an increasing number of variants causing monogenic obesity has been described, mostly genes encoding components of leptin-melanocortin pathways. The accessory protein MRAP2 (Melanocortin Receptor Accessory Protein 2) acts in body weight regulation and its inactivation is associated with early-onset severe obesity in humans, it’s believed that this occurs through both MCR4 (Melanocortin Receptor 4) dependent and independent actions. To date, some studies have shown an association between MRAP2variants with severe obesity. In this present study, we report a 4.9-year-old Brazilian boy, son of a non-consanguineous couple with severe early-onset obesity. He was born at 37.8 weeks gestation, birth weight of 3090g and birth length of 46.5cm, his mother had a history of gestational diabetes, hypertension, and smoker. After birth, the newborn presented neonatal jaundice with no need for phototherapy, and hypoglycemia resolved after formula administration, maintaining mixed feeding. According to the family register, the patient showed higher weight gain from the age of 2 years old, and besides obesity, he also presented hypertension and hyperactivity disorder, in investigation with neuropediatric and nephrologist. At the time of consultation, he presented acanthosis nigricans, increased waist circumference (waist to height ratio = 0.81), and hypertension (blood pressure 120/70 mmHg, above p95 for age), height Z score was -1.62 SD (standard deviation) and BMI 33.89 m², Z score +7.15 SD. Due to early-onset severe obesity, next-generation sequencing (NGS) with specific obesity gene panel (ADCY3, BDNF, GNAS, KSR2, LEP, LEPR, MC4R, MRAP2, NTRK2, PCSK1, POMCe SIM1) was performed. A novel variant in heterozygous was found in MRAP2gene, on chromosome 6 (position 84.772.712, variant c.227+1G>T, OMIM: 615457). This variant was considered deleterious in silico prediction models. The findings in the proband require follow-up of blood pressure, glucose, and cortisol levels, and if available investigation should be extended to parents.