Circulating levels of ghrelin and hyperphagia in patients with rare genetic neurodevelopmental disorders.

Abstract

Hyperphagia, overweight and obesity are frequent in people with rare neurodevelopmental disorders (NDDs). Prader-Willi syndrome (PWS) is a rare NDD with hyperphagia and hyperghrelinemia. To measure ghrelin levels, hyperphagia and caregiver burden in rare NDDs patients to understand pathophysiology and improve care. A single-visit, non-interventional, national, multicenter, cross-sectional study. Seven French reference centers for rare NDDs participated. 130 patients (43% children) with a rare genetic NDD (27 distinct conditions) were included. Their median age was 19.8 years. Three control groups were used for comparison: "PWS" (n=153), "Obese" (n= 49), and "Lean" (n=31) groups. The primary endpoint was ghrelin level (total, acylated (AG), unacylated (UAG)). The first secondary endpoint was hyperphagia questionnaire (HQ) scores. Median total ghrelin levels were 76.7 [22.2-1110.9] pg/mL; median AG levels were 33.7 [8.0-754.3] pg/mL; and median UAG levels were 44.2 [11.5-356.6] pg/mL, which were lower than the PWS group (p<0.001) and no different from the Obese group. The mean HQ total score was 26.3 [10-46] for children and 24.0 [11-52] for adults. The HQ total score was statistically higher in children with NDDs and lower in adults compared to PWS. The mean ZBI score was 37.8 [6-74] in children and 37.6 [2-76] in adults, and was positively correlated with the HQ total score. Ghrelin levels were normal in our study population. Hyperghrelinemia is a biomarker of PWS. Hyperphagia is more prevalent and severe in children with NDDs compared with PWS.