SPG7 and Early-onset spastic ataxia-neuropathy syndrome: This spectrum includes: homozygous loss-of-function mutations in SPG7 resulting in the absence of hetero-oligomeric m-AAA isoenzymes (associated with SPG7); heterozygous loss-of-function mutations in AFG3L2 decreasing the dosage of both homo- and hetero-oligomeric forms of the m-AAA proteases (associated with SCA28); and homozygous AFG3L2Y616C mutations also affecting both isoforms and further reducing the residual cellular m-AAA protease activity (associated with the early-onset spastic ataxia-neuropathy syndrome described here).