Leber syndrome: causes, symptoms, diagnosis, treatment

Leber's syndrome (LHON syndrome - Leber's Hereditary Optic Neuropathy), or hereditary atrophy of the optic nerves, was described by T. Leber in 1871.

Causes and pathogenesis of Leber syndrome. The disease is based on a point mutation of mtDNA. It is most often found at position 11,778 of mtDNA of complex 1 of the respiratory chain. It belongs to the class of miscens mutations, when histidine is replaced by arginine in the structure of the dehydrogenase complex 1 of the respiratory chain. Several other point mutations of mtDNA have also been described in different positions (3460 with the replacement of threonine by alanine in the subunit of complex I and at position 14,484 with the replacement of methionine by valine in subunit 6 of complex 1 of the respiratory chain). Other, additional mutations are also identified.

Symptoms of Leber syndrome. The manifestation of the disease occurs at the age of 6 to 62 years with a maximum of 11-30 years. The development is acute or subacute.

The disease begins with a sharp decrease in vision in one eye, and after 7-8 weeks - in the other. This process is progressive, but complete blindness rarely develops. After a period of sharp decrease in visual acuity, remission and even improvement may occur. The central visual fields are mainly affected, often with scotoma in the central part and preservation of the peripheral sections. Some patients may simultaneously experience pain in the eyeballs when they move.

Vision loss is often combined with neurological symptoms: peripheral neuropathy, tremor, ataxia, spastic paresis, mental retardation. Neuropathy impairs tactile and vibration sensitivity in the distal parts of the limbs, and reduces reflexes (calcaneal, Achilles). Patients often have bone and joint disorders (kyphosis, kyphoscoliosis, arachnodactyly, spondyloepiphyseal dysplasia). Scoliosis is more often observed with mutation 3460. Sometimes ECG changes are detected (prolongation of the Q-T interval, deep Q wave, high R wave).

The fundus shows dilation and telangiectasia of the retinal vessels, edema of the neuronal layer of the retina and the optic disc, and microangiopathy. Morphological examination of the eyes reveals degeneration of the axons of the retinal ganglion cells, decreased density of the myelin sheaths, and proliferation of glia.

When examining muscle fiber biopsies, a decrease in the activity of complex 1 of the respiratory chain is detected.

The diagnosis is confirmed by detection of major mtDNA mutations.

Genetic counseling is difficult due to the maternal mode of inheritance. Anecdotal evidence suggests a high risk for male cousins (40%) and male nephews (42%).

Differential diagnostics are carried out with diseases accompanied by decreased visual acuity (retrobulbar neuritis, optic-chiasmatic arachnoencephalitis, craniopharyngioma, leukodystrophies).

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