The same threshold may also be applied to isolated disorders caused by pathogenic variants in mtDNA including those leading to complex V deficiency; however, smaller reductions may not exclude pathogenicity as seen in VC6 (MT-ND1), VC12 (MT-ND5) and VC20 (MT-ATP6) (Fig. 2D). Here, MT-ND5 is linked to hyperinsulinemic hypoglycemia, familial, 4.