Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide

Abstract

Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity through dysregulation of neuronal pathways in the hypothalamus and prefrontal cortex that regulate hunger and satiety. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury. We show evidence of corneal small fiber degeneration in 2 siblings carrying a heterozygous missense variant c.508A>G, p.Ille170Val in the MC4R gene. Both children were treated with once weekly semaglutide for 6 months with no change in weight, and only a minor improvement in HbA1c and lipid profile. However, there was evidence of nerve regeneration with an increase in corneal nerve fiber density (CNFD) [child A (13.9%), child B (14.7%)], corneal nerve branch density (CNBD) [child A (110.2%), child B (58.7%)] and corneal nerve fiber length (CNFL) [child A (21.5%), child B (44.0%)].

Keywords: GLP-1 - glucagon-like peptide-1; monogenic obesity; nerve regeneration; neurodegeneration; semaglutide.

Figure 1

CCM images of siblings with MC4R mutation before and after treatment vs. healthy control. (A) healthy control, (B) child A before treatment, (C) child A after 6-months treatment with GLP-1, (D) child B before treatment, (E) child B after 6-months treatment with semaglutide.

Figure 2

Corneal nerve parameters in children with MC4R mutation before (red) and after (orange) treatment with semaglutide compared to a healthy control (HC) (green). (A) CNFD, corneal nerve fiber density; (B) CNBD, corneal nerve branch density; (C) CNFL, corneal nerve fiber length.