The nosology of infantile optic atrophy is unclear. There is no doubt that some familial cases with likely autosomal recessive inheritance lacked (or were not tested for) urinary metabolites considered diagnostic for an optic atrophy disorder with 3-methylglutaconate aciduria (258501) and labeled methylglutaconic aciduria type III (and sometimes Costeff optic atrophy syndrome). Excretion of 3-methylglutaric acid may also be increased. But it is also possible that another form of infantile optic atrophy without aminoaciduria also exists. Early onset (early childhood) optic atrophy, with later (second decade) spasticity, ataxia, extrapyramidal signs and cognitive defects to some degree are common to both. Dementia, posterior column signs and peripheral neuropathy are more variable clinical signs. Nerve biopsies and postmortem studies show widespread disease with evidence of chronic neuropathy, neuronal loss, and gliosis. In Behr's report, the neurologic symptoms remained static after a period of progression. Others have reported progression with the majority of patients severely handicapped by the third decade of life.