Also known as Leber optic atrophy, Leber's hereditary optic neuropathy is a genetic disease in which retinal ganglion cells and their axons degenerate and eventually die, leading to an acute painless loss of central vision. Other minor symptoms may appear such as tremors, numbness or weakness in arms and legs, or loss of ankle reflexes. Affecting predominantly young adult males, Leber's hereditary optic neuropathy is only transmitted through the mother. This inherited disease is caused by mutations in the mitochondrial (not nuclear) genome and only the egg contributes mitochondria to the embryo. The mutations which cause Leber optic atrophy are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Thus, men cannot pass on the disease to their offspring.
In Leber's hereditary optic neuropathy, both the retina and the optic nerve stop working properly, which means they stop sending signals or visual information to the occipital lobe of the brain. The rest of the eye keeps working normally, so that light enters the eye through the pupil, passing through the lens to be focused on the retina as it should. Nevertheless, even though the light is focused properly on the retina, in Leber's hereditary optic neuropathy this information is not converted into signals for the brain to process.
Without a known family history of LHON the diagnosis is difficult and usually requires a neuro-ophthalmological evaluation and/or blood testing for DNA assessment that is available only in a few laboratories. Hence the incidence is probably greater than appreciated. The prognosis for those affected is almost always that of continued very severe visual loss. Regular corrected visual acuity and perimetry checks are advised for follow up of affected individuals. There is no accepted treatment for this disease. Genetic counselling should be offered. Optical coherence tomography can be used for more detailed study of retinal nerve fiber layer thickness. Red green color vision testing may detect losses. Contrast sensitivity may be diminished. There could be an abnormal electroretinogram or visual evoked potentials. Neuron-specific enolase and axonal heavy chain neurofilament blood markers may predict conversion to affected status.