Early childhood BMI trajectories inmonogenic obesity

Background. The estimated prevalence of monogenic obesity is 1-5% in severely obese cohorts. Distinguishing between monogenic forms of obesity and common obesity at an early age presents a tremendous challenge for pediatricians. In particular, the question is, when to initiate further investigations. Objective. Can body mass index (BMI) and BMI trajectories be used as parameters for early diagnosis of monogenic obesity due to mutation in leptin or the leptin receptor? Methods. Trajectories of BMI during early childhood (0-5 years) in n = 21 children with monogenic obesity due to leptin deficiency (LEP, n = 6), leptin receptor deficiency (LEPR, n = 6), and MC4 receptor deficiency (MC4R, n = 9) were analyzed. BMI values were compared at 2 years and 5 years of age, the time points of two compulsory pediatric examinations in Germany. Results. Patients with functional leptin deficiency or leptin receptor deficiency showed a tremendous increase in BMI during the first 2 years of life. Their BMI was >25 kg/m(2) (27.2-38.4 kg/m(2)) at the age of 2 years and >30 kg/m(2) (33.3-45.9 kg/m(2)) at the age of 5 years. MC4 receptor-deficient patients had a later onset of obesity, with significantly lower BMI values at 2 and 5 years (p < 0.01). Conclusion. Our results show that BMI values >25 kg/m(2) at the age of 2 years and >30 kg/m(2) at the age of 5 years are indicators for monogenic obesity due to a mutation in the leptin gene or leptin receptor gene. For these patients, further investigations should be carried out at an early stage (measurement of circulating leptin, bioactive leptin, and molecular genetics).