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Bulgarian Review of Ophthalmology

Leber`s hereditary optic neuropathy

S. Cherninkova


Leber`s hereditary optic neuropathy (LHON) is a rare maternally inherited disease caused by mitochondrial DNA point mutations in genes encoding the MT-ND1, MT-ND4, MT-ND4L and MTND6 subunits of complex I in the mitochondrial respiratory chain. The most common mutations G11778A in MT-ND4 gene, G3460A in MT-ND1 gene and T14484C in MT-ND6 gene cause the disease in 90% of patients but there are also a number of less common mutations. LHON is characterized by bilateral acute or subacute optic neuropathy and usually occurs in young males. The common age at onset of visual failure is in second or third decade. The visual acuity is markedly diminished and the typical perimetric ? nding is bilateral central scotoma. Ophthalmoscopy reveals optic disc hyperemia, tortuous, telangiectatic peripapillary retinal vessels in the acute stage of LHON but bilateral optic atrophy after the acute stage is present. Recently the synthetic analogue of coenzyme Q10 Idebenone is an approved drug for LHON patients. Idebenone acts as an electron carrier transferring electrons directly to the complex III of the mitochondrial respiratory chain. In this way the production of mitochondrial adenosine triphosphate increases and the retinal ganglion cells are protected from oxidative damage.


Leber`s hereditary optic neuropathy; neuro-ophthalmological symptomatology; genetic investigation

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Bi, R., Zhang, A., Jia, X., Zhang, Q., Yao, Y. Complete mitochondrial DNA genome sequence variation of Chinese families with mutation m.3635G>A and Leber hereditary optic neuropathy. Mol Vis, 2012, 18, 3087-3094.

Blaak, E. Gender differences in fat metabolism. CurrOpinClinNutrMetab Care, 2001,4, 6, 499-502.

Buchan, J., Ong, C., Dabbs, T. Acute Leber hereditary optic neuropathy in a 73-yearold man. Eye,2007, 21, 2,859-860.

Carelli,V., d`Adamo, P., Valentino, M., La Morgia, C., Ross-Cisneros, F., Caporali, L., Maresca, A., LoguercioPolosa, P., Barboni, P., De Negri, A., Sadun, F., Karanjia, R., Salomao, S., Berezovsky, A., Chicani, F., Moraes, M., MoraesFilho, M., Belfort, R. Jr, Sadun, A. Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion. Brain, 2016, 139, 3, e17.

Caroll, W., Mastaglia, F. Leber`s optic neuropathy: a clinical and visual evoked potentials study of affected and asymptomatic members of a six generation family. Brain, 1979, 102, 3, 559-580.

Dimitriadis, K., Leonhardt, M., Yu-Wai- Man, P., Kirkman, M., Korsten, A., De Coo, I., Chinnery, P., Klopstock, T. Leber`s hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients. Orphanet J Rare Dis, 2014, 9, Oct 23, 158.

Fraser, J., Biousse, V., Newman, N. The neuro-ophthalmology of mitochondrial disease. SurvOphthalmol, 2010, 55, 4, 299-334.

Giordano, C., Montopoli, M., Perli, E., Orlandi, M., Fantin, M., Ross-Cisneros, F., Caparrotta, L., Martinuzzi, A., Ragazzi, E., Ghelli, A., Sadun, A., d'Amat,i G., Carelli, V. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy. Brain, 2011, 134, 1, 220-234.

Harding, A., Sweeney, M., Govan, G., Riordan-Eva, P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am J Hum Genet, 1995, 57, 1, 77-86.

Howell, N. Leber hereditary optic neuropathy: respiratory chain dysfunction and degeneration of the optic nerve. Vis Res, 1998, 38, 10, 1495-1504.

Kerrison, J., Newman, N. Clinical Spectrum of Leber's Hereditary Optic Neuropathy. Clin Neuroscience, 1997, 4, 5, 295-301.

Kirkman, M., Korsten, A., Leonhardt, M., Dimitriadis, K., De Coo, I., Klopstock, T., Griffiths, P. , Hudson, G., Chinnery, P., Yu-Wai- Man, P. Quality of life in patients with Leber hereditary optic neuropathy. Invest Ophthalmol Vis Sci, 2009, 5, 7, 3112-3115.

Klopstock, T., Yu-Wai-Man, P., Dimitriadis, K., Rouleau, J., Heck, S., Bailie, M., Atawan, A., Chattopadhyay, S., Schubert, M., Rummey, C., Metz, G., Leinonen, M., Griffiths, P., Meier, T., Chinnery, P. A randomized placebo-controlled trial of idebenone in Leber`s hereditary optic neuropathy. Brain, 2011, 134, 9, 2677-2686.

Lyseng-Williamson, K. Idebenone: A review in Leber`s hereditary optic neuropathy. Drugs, 2016, 76, 7, 805-813.

Mackey, D., Oostra, R., Rosenberg, T., Nikoskelainen, E., Bronte-Stewart, J., Poulton, J., Harding, A., Govan, G., Bolhuis, P., Norby, S. Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. Am J Hum Genet, 1996, 59, 2, 481-485.

Martikainen, M., Ng, Y., Gorman, G., Alston, C., Blakely, E., Schaefer, A., Chinnery, P., Burn, D., Taylor, R., McFarland, R., Turnbull, D. Clinical, genetic, and radiological features of extrapyramidal movement disorders in mitochondrial disease. JAMA Neurol, 2016, 73, 6, 668-674.

Matthews, L., Enzinger, C., Fazekas, F., Rovira, A., Ciccarelli, O., Dotti, M., Filippi, M., Frederiksen, J., Giorgio, A., Küker, W., Lukas, C., Rocca, M., De Stefano, N., Toosy, A., Yousry, T., Palace, J. MRI in Leber's hereditary optic neuropathy: the relationship to multiple sclerosis. J NeurolNeurosurg Psychiatry, 2015, 86, 5, 537-542.

McFarland, R., Chinnery, P., Blakely, E., Schaefer, A., Morris, A., Foster, S., Tuppen, H., Ramesh, V., Dorman, P., Turnbull, D., Taylor, R. Homoplasmy, heteroplasmy, and mitochondrial dystonia. Neurology, 2007, 69, 9, 911-916.

Nikoskelainen, E., Hoyt, W., Nummelin, K. Ophthalmoscopic findings in Leber`s hereditary optic neuropathy.I. Fundus findings in asymptomatic family members. Arch Ophthalmol, 1982, 100, 10, 1597 1602.

Nikoskelainen, E., Hoyt, W., Nummelin, K. Ophthalmoscopic findings in Leber`s hereditary optic neuropathy.II. The fundus findings in the affected family members. Arch Ophthalmol, 1983, 101, 7, 1059-1068.

Nikoskelainen, E., Hoyt W., Nummelin, K. Fundus findings in Leber`s hereditary optic neuroretinopathy. Ophthalmic Paediatr Genet, 1985, 5, 1-2, 125-130.

Online 'Mendelian Inheritance in Man' (OMIM) LEBER OPTIC ATROPHY -535000

Pott, J., Wong, K. Leber's hereditary optic neuropathy and vitamin B12 deficiency. Graefes Arch ClinExpOphthalmol, 2006, 244Z, 10, 1357-1359.

Power, M., Schulkin, J. Sex differences in fat storage, fat metabolism, and the health risks from obesity: possible evolutionary origins. Br J Nutr, 2008, 99, 5, 931-940.

Puomila, A., Hämäläinen, P., Kivioja, S., Savontaus, M., Koivumäki, S., Huoponen, K., Nikoskelainen, E.Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland. Eur J Hum Genet, 2007, 15, 10, 1079-1089.

Riordan-Eva, P., Sanders, M., Govan, G., Sweeney, M., Da Costa, J., Harding, A. The clinical features of Leber`s hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain, 1995, 118, 2, 319-337.

Sadun, A., Carelli, V., Salomao, S., Berezovsky, A., Quiros, P., Sadun, F., DeNegri, A., Andrade, R., Moraes, M., Passos, A., Kjaer, P., Pereira, J., Valentino, M., Schein, S., Belfort, R.Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy. Am J Ophthalmol, 2003, 136, 2, 231-238.

Shu, L., Zhang, Y., Huang, X., Chen, C., Zhang, X. Complete mitochondrial DNA sequence analysis in two southern Chinese pedigrees with Leber hereditary optic neuropathy revealed secondary mutations along with the primary mutation. Int J Ophthalmol, 2015, 5, 1, 28-31.

Vladimirova, Z., Todorova, A., Zaharova, B., Cherninkova, S. Leber`s disease withG3635A mutation. Ophthalmology Times, 2014, 10, 1, 39-41.

Volodko, N., L`vova. M., Starikovskaya, E., Derbeneva, O., Byshkov, I., Mikhailovskaya, I., Pogozneva, F., Fedotov, F., Soyan, G., Procaccio, V., Wallace, D., Sukernik, R. Spectrum of pathogenic mtDNA mutations in Leber`s hereditary optic neuropathy families from Siberia. Russian J Genet, 2006, 42, 1, 89-97.

Wallace, D., Singh, G., Lott, M., Hodge,J., Schurr, T., Lezza, A., Elsas, L., Nikoskelainen, E. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science, 1988,242, 4884, 1427-1430.

Yang, J., Zhu, Y., Tong, V., Chen, L., Liu, L., Zhang, Z., Wang, X., Huang, D., Qui, W., Zhuang, S., Ma, X.Confirmation of the mitochondrial ND1 gene mutation G3635A as a primary LHON mutation. Biochemical and Biophysical Research Communication, 2009, 386, 50-54.

Yu-Wai-Man, P., Turnbull, D., Chinnery, P. Leber hereditary optic neuropathy. J Med Genet, 2002, 39, 3, 162-169.

Yu-Wai-Man, P., Griffiths, G., Brown, D., Howell, N., Turnbull, D., Chinnery, P. The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England. Am J Hum Genet, 2003, 72, 2, 333-339.

Yu-Wai-Man, P., Griffiths, P., Chinnery, P. Mitochondrial optic neuropathies-Disease mechanisms and therapeutic strategies. Prog Retinal Eye Res, 2011, 30, 2, 81-114.

Yu-Wai-Man, P., Votruba, M., Moore, A., Chinnery, P.Treatment strategies for inherited optic neuropathies: past, present and future. Eye, 2014, 28, 5, 521-527.



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About The Author

S. Cherninkova
Clinic of Nervous diseases, University Alexandrovska Hospital, Medical University, Sofia