ESPE Abstracts

Introduction: The hypothalamic melanocortin-4 receptor (MC4R) pathway plays a vital role in energy balance. Genetic defects in the MC4R pathway may result in severe early onset obesity.

Objective: The TEMPO registry (NCT03479437) aims to identify and enroll approximately 1000 participants with rare genetic forms of obesity that are potentially related to key genes, upstream or downstream, of the MC4R. In addition, the TEMPO registry will evaluate the burden of disease on participants, caregivers, health care providers and the health care system.

Study Design and Population: The TEMPO registry is a voluntary, prospective, open-ended, registry. Participants must meet both phenotypic and genotypic entry criteria. Participants aged ≥2 years with severe obesity, defined as BMI >40 mg/kg² (for participants ≥18 years) or BMI that is >1.4 x the corresponding age/sex 95th percentile (in children 2–17 years) are eligible for inclusion. Participants must possess at least one of the following genotypes: 1) Bi-allelic (homozygous or compound heterozygous) POMC, PCSK1 or LEPR pathogenic or likely pathogenic variants, or encoding a subset of variants of unknown significance, leading to either clinical POMC or LEPR deficiency obesity; 2) Presence of pathogenic, likely pathogenic or a subset of variants of unknown significance in at least 2 genes in the pathway (a composite genotype); 3) Presence of other high-confidence, high-impact genetic variations in the MC4R gene or other MC4R pathway genes carried by non-syndromic participants with severe obesity. Participants with recognized syndromic forms of obesity will be excluded.

Methodology: Data sources will include electronic surveys completed by adult and minor (aged 13–17) participants, caregivers for all minors and healthcare providers. Surveys will be completed at study entry (baseline) and annually thereafter. Surveys will collect demographics, results of genetic testing, medical/family history, disease characteristics, resource utilization, eating habits/hunger episodes, quality of life, and burden of disease on participants, caregivers, healthcare providers and the healthcare system.

Conclusions: The TEMPO registry will enable the identification of patients with rare forms of severe early-onset obesity resulting from rare genetic variants in the MC4R pathway. This registry will provide insights into the overall course and disease burden of genetic disorders presenting with these extreme obesity features.