ESPE Abstracts

Background: Leptin receptor (LEPR) deficiency is a rare genetic disorder that causes severe early-onset obesity. Most children with this condition are obese before the age of one. Leptin and LEPRs are needed for the regulation of appetite and body weight. The most common symptom, present in 96% of patients, is impaired appetite regulation, also known as hyperphagia. Other clinical features include pituitary hormone disorders; such as hypogonadotropic hypogonadism, central hypothyroidism and growth hormone deficiency; hyperinsulinemia or frequent infections.

Case report: A four-month-old girl was admitted to our pediatric endocrinology unit for evaluation of obesity. Her family history was unremarkable except her parents’ consanguineous marriage. She was born at term with a birth weight of 3,070 g (0.3 SDS) as a second child of healthy second-degree cousin parents. Her neuromotor development was compatible with her age. Her parents reported that she started to gain weight after 2 months of age. Her weight, length and body mass index (BMI) on admission were 11.1 kg (4.73 SD), 62 cm (-0.45 SD) and 28.8 kg/m2 (5.91 SD), respectively. She was exclusively breastfed, but had a sense of hunger. At 6 months of age, her weight, height and BMI were 13.9 kg (5.39 SDS), 69.6 cm (1.17 SDS) and 28.8 kg/m2 (5.37 SDS), respectively. Physical examination was unremarkable. She suffered from severe early onset obesity and hyperphagia. Therefore, her weight gain was progressive. Initial laboratory investigations revealed normal blood count, electrolytes and liver-kidney and thyroid functions. Hyperlipidaemia was found in her laboratory results. Next generation sequencing (NGS), identified a novel homozygous (NM_002303.6) LEPR variant (c.1603+1del), which was predicted to have ‘Likely Pathogenic’ according to American College of Medical Genetics (ACMG) criterias. Moreover, this variant has not been identified in HGMD (http://www.hgmd.cf.ac.uk) and the Exome Aggregation Consortium (ExAC). Segregation analysis was planned. So far she has not shown any signs of hyperinsulinemia or pituitary hormone deficiency or immune deficiency. She has no signs of puberty; therefore hypogonadotropic hypogonadism cannot be excluded yet. Cardiac examination and Echocardiography were unremarkable.

Conclusion: LEPR deficiency is caused by variants in the LEPR gene. As there are several inherited conditions that include excessive hunger and early onset obesity, genetic testing may be used to help make a specific diagnosis. Advances in molecular genetic technologies are helping to identify the etiology of early-onset obesity, and the implementation of genetic diagnosis in clinical practice may enable a personalised medicine approach.