Melanocortin-4 receptor signaling is not required for short-term weight loss after sleeve gastrectomy in pediatric patients

Homozygous or compound heterozygous melanocortin-4 receptor (MC4R) mutations are rare with fewer than 10 patients described in current literature. Here we report the short- and long-term outcomes for four children ages 4.5-14 who are homozygous for loss-of-function mutations in the MC4R and underwent laparoscopic sleeve gastrectomy. All four patients experienced significant weight loss and improvement in, or resolution of, their comorbidities in the short term. One patient, however, has had significant weight regain in the long term. We conclude that MC4R signaling is not required for short-term weight loss after laparoscopic sleeve gastrectomy in children. Behavior modification may be more important for long-term weight maintenance, but patients with homozygous MC4R deficiency should not be excluded from consideration for sleeve gastrectomy. However, as at least one copy of functional MC4R is necessary and sufficient to induce long-term postoperative weight loss benefits, patients with complete loss of MC4R functionality might be less likely to exhibit the same benefits resulting from bariatric surgery.