MUTATIONS OF LEBER’S HEREDITARY OPTIC NEUROPATHY AND THEIR ASSOCIATION WITH CLINICAL MANIFESTATION

Abstract

Leber‘s hereditary optic neuropathy (LHON) is a rare disorder that mainly presents in males in their young age. The majority of cases are caused by three primary maternally inherited mtDNA point mutations (m.3460G > A, m.11778G > A, and m.14484T > C) that affect su­bunits 4, 6, and 1 of NADH dehydrogenase, respecti­vely. It impairs glutamate transport and increases re­active oxygen species production, leading to apoptosis of ganglion cells, atrophy and demyelination of optic nerves, chiasm and pathways. This leads to visual dis­turbances such as painless, subacute or acute loss of central vision, initially in one eye and after few weeks or months in the other eye. The clinical expression of LHON depends on the primary mutations. M.3460G > A and m.11778G > A have been reported to have se­vere visual impairment and poor visual recovery, while m.14484T > C has the best long-term visual outcome with a better partial visual recovery rate. In some ca­ses, it is observed that LHON may also manifest in extraocular symptoms, such as cardiac, skeletal, or ne­urological abnormalities. Currently, ibedenone is the only approved drug that prevents regression of visual function and improves it. The aim of this article is to discuss etiology and pathogenesis, clinical expression according to mtDNR mutation, treatment, and response to treatment according to mtDNA mutation.