be classified into pure and complicated forms, depending on whether additional clinical features are present besides spastic paraplegia, such as optic atrophy, ataxia, peripheral neuropathy, extrapyramidal deficits, and cognitive decline. Friedreich's ataxia (FA) FA is an autosomal recessive disorder caused by pathological GAA trinucleotide repeat expansions in the FXN gene. The encoded protein frataxin is directed to the mitochondrial inner membrane and is involved in the assembly of iron-sulphur cluster, which are a critical component of the mitochondrial respiratory chain complexes. In a recent study of 26 patients with confirmed FA, all patients had evidence of optic nerve dysfunction, although only five were visually symptomatic. The optic neuropathy differed from that of LHON or DOA, displaying a pattern of retinal nerve fiber layer (RNFL) loss and no preferential involvement of papillomacular bundle. Mitochondrial encephalomyopathies Includes Mitochondrial Encephalitis Lactic Acidosis Seizures (MELAS), myoclonic epilepsy and ragged red fibers (MERRF), maternally inherited Leigh syndrome (MILS), and mitochondrial neurograstrointestinal encephalomyopathy (MNGIE), all of which can all develop optic neuropathies, although it is usually a secondary feature overshadowed by more prominent neurological features. Overlapping phenotypes As our understanding of mitochondrial diseases improves a degree of similarity and overlap are seen within this group of disorders. For example, in some OPA1 carriers, patients will develop neurological features indistinguishable from HSP while others develop a pattern of peripheral neuropathy with a similar disease course to CMT, and still others will develop a prominent cerebellar syndrome consistent with FRDA. Pathophysiology Even though dysfunction of the mitochondria can be either congenital or acquired, both causes share a common pathophysiology: an impairment of oxidative phosphorylation within the mitochondria, which leads to a decrease of ATP production and a simultaneous increase in ROS. These mitochondria are made within the central somata of the retinal ganglion cell, transported down axons, and distributed where they are needed. Efficient transportation of mitochondria depends on multiple factors, including their own energy production, the integrity of the cytoskeleton and its protein components (tubulin, etc.), and adequate myelination of the axons. Any dysfunction of these systems may be of pathological relevance for optic neuropathies with primary or secondary involvement of mitochondria. Genetic mutations, toxic insult, and nutritional depletion can all have a negative impact on the structure and function of mitochondria within the optic system, resulting in this type of neuropathy. Diagnosis A thorough history is essential and should cover family history, diet; drug/toxin exposure social