It was found that rather than mutations in traditionally associated COX subunits, the family was affected by homozygous donor splice site mutations in NDUFA4, resulting in protein loss-of-function, with the further suggestion that families suffering from unexplained COX deficiency should be screened for NDUFA4 mutations. The gene discussed is COXFA4; the disease is hyperinsulinemic hypoglycemia, familial, 4.