Mutations in genes belonging to the melanocortin-4 receptor (MC4R) pathway are linked to severe obesity but these cases are generally under-diagnosed and poorly understood.
Therefore, a new registry, called TEMPO, has been set up to collect data from these patients with the goal of using it as a platform to help researchers investigate further the link between certain genetic mutations and obesity.
The plans and protocol to be used in the registry were described in a study, “Tracing the effect of the melanocortin-4 receptor pathway in obesity: study design and methodology of the TEMPO registry,” which was published in the journal The Application of Clinical Genetics.
The MC4R signaling pathway plays a key role in body weight, since it regulates food intake and energy expenditure. Activation of MC4R, which is present in the hypothalamus — the brain region that controls appetite — decreases food intake, enhances energy expenditure, and ultimately supports weight loss.
Mutations in genes of this signaling pathway may promote early-onset severe obesity and insatiable hunger (medically called hyperphagia). Alstrom syndrome and Bardet-Biedl syndrome are two diseases linked to MC4R-related mutations and obesity.
Researchers estimate that up to 6% of obese individuals are MC4R-deficient. MC4R pathway deficiency can be identified early on, and targeted treatment strategies can help improve the quality of life of those affected.
To gain better insight on the incidence and impact of MC4R-pathway impairment, researchers have set up the TEMPO registry (NCT03479437), a prospective study that aims to recruit volunteers with early-onset severe obesity due to mutations in genes involved in the MC4R pathway.
The registry is currently recruiting participants at the Nationwide Children’s Hospital in Ohio, and is expected to include sites in Canada and across Europe in the future.
Enrollment is open to individuals who are 2 years or older with a body mass index (BMI), a measure of body fat, in agreement with clinical criteria for severe obesity. Participants must also carry mutations in the MC4R gene pathway.
The participant or a parent/caregiver will fill out online surveys about their quality of life through the Impact of Weight on Quality of Life-Kids and Pediatric Quality of Life Inventory Family Impact Module questionnaires, together with questions specifically developed by an advisory board to evaluate the needs, eating characteristics, and burden of individuals with rare genetic disorders of obesity.
Enrolled participants will be contacted every year to complete follow-up surveys.
Also, the participant’s healthcare provider will conduct clinical assessments when joining the registry and annually thereafter, in which they will collect the patient’s demographic data (age, race, and gender), medical history, as well as eating habits and hunger episodes, among other parameters.
Under the scope of the registry, all participants will undergo genetic testing for mutations in major genes of the MC4R pathway that are associated with obesity.
“The TEMPO registry will provide insights into the overall course and disease burden for individuals with rare genetic disorders of obesity,” the researchers wrote.
“Health care providers may use this resource to improve the identification, diagnosis, and treatment of individuals with rare forms of genetic obesity,” they concluded.
For more information about the TEMPO registry, visit its webpage here.