The existence of some very-low-level wild-type NDUFA4 transcripts in patients harboring the c.42+1G → C mutation might explain the slower natural history and the comparatively milder clinical phenotype observed; most previously reported patients with nuclear-encoded COX deficiency exhibit severe phenotypes resulting in early childhood death. This evidence concerns the gene COXFA4 and hyperinsulinemic hypoglycemia, familial, 4.