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

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, noninterventional, national, multicenter, cross-sectional study.

Seven French reference centers for rare NDDs participated.

A total of 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, unacylated). The first secondary endpoint was hyperphagia questionnaire (HQ) scores.

Median total ghrelin levels were 76.7 (22.2-1110.9) pg/mL; median acylated levels were 33.7 (8.0-754.3) pg/mL; and median unacylated levels were 44.2 (11.5-356.6) pg/mL, which were lower than the PWS group (P < .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 Zarit Burden Interview 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.