Leber Hereditary Optic Neuropathy

Summary: • Leber Hereditary Optic Neuropathy: mitochondrially inherited o Does not manifest at birth, typically presents in young adult male patient o Unclear why males more affected than females who also inherit maternal mitochondrial deletion -Possible exogenous factors i.e. Nuclear cofactor, hormonal cofactor, smoking, alcohol • May be more prominent in males than females and precipitate mitochondrial threshold effect in Leber o;Passed on by mothers, so affected males cannot pass mitochondrial deletion on to descendants while females can o Mutations at positions 11778, 3460, and 14484 account for 95% of mutations in Leber patients -Remaining 5% found by sequencing entire mitochondrial DNA • Presentation: typically, young male o Acute unilateral -bilateral sequential or simultaneous central vision loss -Central or cecocentral scotoma -Initially- slightly hyperemic optic disc, pseudo edema -No leaking with fluorescein angiogram o Over time, development of optic atrophy and loss of maculopapular bundle • Diagnosis: o Imaging to rule out optic neuritis and NMO o Screen 11778, 3460, and 14484 -14484- most likely to recover -11778- most common but least likely to recover -3460- somewhere in between • Treatment: no real treatment for Leber Hereditary Optic Neuropathy o Mitochondrial supplements including Coenzyme Q10 o Study on idebenone with modest effects but not available in United States o Avoid mitochondrial precipitants- smoking, alcohol, marathon running, etc. o Ongoing clinical trial recruiting for adeno-associated viral vector gene therapy -In very early stages o Genetic counseling- male patients cannot pass mitochondrial deletion on to descendants but must inform maternal line relatives of their risk