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At a glance

It is a rare hereditary form of optic atrophy that usually affects young males. Characterized by sudden bilateral cloudiness of vision, followed by scotoma, rapid deterioration of central vision, and occasional color vision disorders. Associated with atrophy of the optic nerve fibers and retinae. Considered a mitochondrial disease. Cardiac conduction defects have been reported with this condition. Blindness is usually seen before the age of 40 years.

Synonyms

Leber Disease; Leber Optic Atrophy.

N.B.: Do not confuse with Leber congenital amaurosis that is another inherited condition described by Dr von Leber. It also involves the retinal system but without mitochondrial DNA implication. It is resulting from a genetic mutation in the CRX gene.

History

Originally described by Theodore von Leber (1840-1917), a German Ophthalmologist, in the 19th century.

Incidence

The exact incidence has not been established; however, it is presumed at 1:50,000 live births. It is reported worldwide. There is a male predominance (2:1).

Genetic inheritance

Genetic disorder related to mitochondrial deoxyribonucleic acid (DNA) transmission (ie, exclusively from mother to child, either male or female). At least four mutations in mitochondrial DNA (including G11778A, T14484C, and G3460A) are associated with this clinical abnormality. Different family pedigrees show different mutations but with clinically similar pictures. The pattern of transmission within a kindred is not in accordance with mendelian principles, and it is apparent that a complex mechanism of inheritance is in operation. The disease is never transmitted by affected men; it is transmitted by affected women or, most frequently, by female carriers of the gene.

Pathophysiology

The mutation in mitochondrial DNA results in lowering of the amount of energy available to the cells of the optic nerve and retina, thus leading to severe cell damage. Fundal changes are described as opacification of the disc margin, hyperemia of the disc vessels, circumpapillary telangiectatic microangiopathy, and swelling of the peripapillary nerve fiber layer.

Diagnosis

Visual field testing reveals enlarging centrocecal scotoma. Fluorescein angiography shows pseudoedema of the nerve fiber layer, peripapillary telangiectasia, and increased tortuosity of the retinal vessels. Pattern electroretinogram and visual-evoked potentials show optic nerve dysfunction not associated with retinal disease. Magnetic resonance imaging may reveal a high signal within the optic nerves. Molecular genetic testing for the mutations can be decisive.

Clinical aspects

There is a wide spectrum of ages at onset of the disorder. However, the most frequent age at onset is in the late teens. Typically, vision fails from normal to severely impaired over a period of weeks, beginning with one eye and then the other eye a few weeks later. Some improvement may occur over months or years; however, vision is permanently impaired. There is probably ...

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