Many cases of isolated Complex I deficiency associated with nuclear gene mutations are discrete entities and no common variant accounts for more than a few apparently unrelated cases.25 We present 10 patients from 8 families who harbour the same homozygous NDUFB3 variant and share a plethora of unifying physical features, an unprecedented finding in association with isolated Complex I deficiency. This evidence concerns the gene NDUFB3 and hyperinsulinemic hypoglycemia, familial, 4.