Walsh & Hoyt: Mitochondrial Disorders

The prototype for a mitochondrial abnormality resulting in optic nerve dysfunction is, of course, LHON, with its classically isolated optic nerve involvement and its causal relationship to mtDNA point mutations. Additionally, Kjers DOA likely results from perturbations of mitochondrial function secondary to abnormalities in a nuclear gene whose product is destined for the mitochondria. Other multisystem hereditary disorders with prominent optic nerve involvement, such as Wolframs syndrome, may also prove to have a final common pathway in mitochondrial dysfunction. Indeed, this apparent selective vulnerability of the ganglion cell or its axon to both hereditary and acquired mitochondrial abnormalities suggests a possible common pathophysiology for these disorders. Given this relative selective involvement of the optic nerve in these disorders, however, it is somewhat surprising that other mitochondrial disorders do not regularly manifest optic neuropathies. Other presumed mitochondrial disorders of both nuclear and mitochondrial genomic origins may manifest optic atrophy, but often only as a secondary clinical feature that is variably present.