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. This evidence concerns the gene COX5A and hyperinsulinemic hypoglycemia, familial, 4.