The most severe form of RRM2B-related mitochondrial disease is associated with mitochondrial DNA depletion (Bourdon et al., 2007; Bornstein et al., 2008; Acham-Roschitz et al., 2009; Kolberg et al., 2009; Spinazzola et al., 2009). This evidence concerns the gene RRM2B and inborn mitochondrial metabolism disorder.