RTN4IP1 mutation and endocrine failure: clinical features and possible benefits of coenzyme Q10

RTN4IP1 encodes a mitochondrial oxidoreductase essential for coenzyme Q biosynthesis; pathogenic variants have been reported mainly in optic neuropathy and encephalopathy. We describe a 30-year-old woman carrying three novel pathogenic RTN4IP1 variants by exome sequencing (c.1163G>A p.Arg388Gln, c.949A>C p.Met317Leu, and c.1109T>C p.Phe370Ser), who presented with panhypopituitarism, optic nerve hypoplasia, corpus callosum agenesis, bicuspid aortic valve disease, seizures, and muscle pain, already on conventional hormone replacement. Coenzyme Q10 (CoQ10) (200 mg) was administered orally for six months; outcomes were assessed using BPI, WOMAC, TUG, LEFS, grip-strength dynamometry, SF-36, CPK, and LDH, and after six months of daily 200 mg CoQ10, the patient showed marked reductions in pain (BPI 4 → 0.8; -80%) and muscle-damage markers (CPK 254 → 110 U/L) together with gains in grip strength (+49%) and lower-extremity function (LEFS 31 → 60; +94%). SF-36 domains related to physical health showed marked gains, while emotional scores remained stable. This is the first report linking RTN4IP1 mutations to endocrine failure and suggesting a therapeutic role for CoQ10 in mitochondrial-related endocrine disease.