ESPE Abstracts

Introduction: The role of genetics in obesity is a much under discussed area. Whilst it is undeniable that environmental factors play a major role in obesity in most cases, there is a small proportion of cases where genetic mutations are the main underlying cause. This includes novel monogenic conditions involving mutations in the Melanocortin-4 receptor (MC4R) signalling pathway. In a healthy individual, the post-meal increase in leptin (LEP) stimulates melanocyte stimulating hormone (MSH) production from Proopiomelanocortin (POMC), and MSH binds MC4Rs to induce satiety and increase energy expenditure. Malfunction of this pathway can lead to obesity.

Aim: The aim of this retrospective study was to look for common features in children and young people (CYP) with MC4R/LEP mutations, which could prompt early specialist referral to establish a genetic diagnosis and help formulate a management plan.

Methods: We carried out a retrospective data collection using LORENZO which is the Hull University Teaching Hospitals (HUTH) trust main database and the HUTH paediatric departmental database. We identified 5 patients with known MC4R/LEP mutations managed by the HUTH trust for obesity, with initial presentations between 1999–2017. The Cambridge Genetics of Obesity Study (GOOS) request form was used as a model to create the data collection template.

Results: 4 patients had MC4R mutations and 1 had a LEP mutation. The CYP presented between ages of 7 months and 11 years, with BMIs over +3SDs for their ages. 2 had heights over +2SDs for their ages. Birth weights for 4 of the patients were low or appropriate for gestation, whilst 1 was large for gestation. All 4 patients with the MC4R mutations had family history of significant obesity in one of the parents. All patients exhibited food seeking behaviours and hyperphagia from early childhood (1–4 years of age). None of the participants had dysmorphic facies or hypogonadism. 3 patients had mental health problems, including self-harming behaviours.

Conclusions: CYP with MC4R mutations may not always be identifiable based on birth weight or tall stature. Although autosomal dominant history of obesity is present among parents, this may not be a distinguishing feature. Early onset food-seeking behaviour and lack of satiation should alert primary care practitioners and general paediatricians towards the possibility of a genetic cause of obesity. Clinicians should also be aware of the high incidence of mental health problems in this cohort of CYP, and consider early referral for psychological support.