Leber's 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.

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

Symptoms of Leber's syndrome. Manifestation of the disease occurs at the age of 6 to 62 years with a maximum of 11-30 years. Development is acute or subacute.

The disease begins with an acute loss of vision in one eye, and after 7-8 weeks - and on the other. This process has a progressive nature, but complete blindness develops rarely. After a period of sharp reduction in visual acuity, remission and even improvement may occur. The central fields of vision, often with the scotoma in the central part and the safety of the peripheral parts, suffer mainly. At a part of patients simultaneously there can be pains in eyeballs at their movement.

Reduced vision is often combined with neurological symptoms: peripheral neuropathy, tremor, ataxia, spastic paresis, mental retardation. With neuropathy, tactile, vibration sensitivity in the distal parts of the limbs is disrupted, a decrease in reflexes (heel, Achilles) is observed. Often in patients, bone-joint disorders (kyphosis, kyphoscoliosis, arachnodactyly, spondyloepiphysic dysplasia) are detected. Scoliosis is observed more often with a mutation of 3460. Occasionally, ECG changes (prolongation of Q-T interval, deep Q tooth, high R tooth ) are observed .

On the fundus there is an expansion and telangiectasia of the retinal vessels, edema of the neuronal layer of the retina and the optic nerve disk, microangiopathy. Morphological examination of the eyes determines the degeneration of axons of ganglion cells of the retina, a decrease in the density of myelin sheaths, and the proliferation of glia.

In the study of muscle fiber biopsies, the activity of the respiratory chain 1 complex was found to decrease.

The diagnosis is confirmed when the main mutations of mtDNA are detected.

Genetic counseling is difficult due to the maternal type of inheritance. Some empirical evidence indicates a high risk for cousins (40%) and male nephews (42%).

Differential diagnosis is performed with diseases accompanied by reduced visual acuity (retrobulbar neuritis, optic-chiasmal arachnoencephalitis, craniopharyngioma, leukodystrophy).

[1], [2], [3], [4], [5]