Introduction
Leber's hereditary optic neuropathy (LHON)It is a maternal inheritance or mitochondrial inheritance caused by a mutation in the mitochondrial DNA 11778, 14484 or 3460. It is a common type of hereditary optic neuropathy.
Cause
(1) Causes of the disease
At present, the site mutation of mitochondrial DNA is considered to be a specific symptom of LHON. 25 site mutations have been reported in foreign countries. It is generally accepted that the primary mutation site has 11778 (G→A) accounted for 40%, and 3460 (G→A) accounted for 6% to 25% and 14484 (T→C) account for 10% to 15% of the three, which can cause disease alone and are not found in the normal population. In 1991, Huoponen et al first found 3460 mutations in the N41 gene, and in 1992 the following year, John et al found 14484 mutations. China's LHON11778 site mutation accounted for 66%, but it is rare. Site mutations are thought to be closely related to LHON, and a small number of 4146 and 14459 point mutations are considered to be major pathogenic mutations associated with LHON.
(two) pathogenesis
LHON secondary sites have increased in recent years, reaching 22, although their incidence in LHON patients is higher than in the control group, but also in the control family, it is generally considered to be polymorphism, the mother found differences It is qualitative and does not cause disease when it exists alone. Some people think that the secondary site can not change the performance of the disease, but some people think that it can enhance the possibility of phenotypic expression, can play a mediating role or have low risk.
symptom
The genetic commonality of the disease is maternal inheritance and tends to male morbidity. Clinically, it can be divided into preclinical, acute and subacute, and chronic atrophy. It is characterized by painless optic neuropathy, and the visual acuity in the acute phase can be drastically reduced to the index only. Although the visual acuity decreased to a different extent, most (98%) were around 0.1, and few were blind. Spontaneous visual recovery can exist, especially in childhood, and is associated with mutations at different sites. The optic disc is congested, with telangiectasia and nerve fiber swelling around the disc, and the retinal arteries and veins are distorted and expanded to varying degrees. There are various types of visual field anomalies, most of which are center dark spots and side center dark spots. Color vision disorder is often acquired, the condition is improved, and the color vision disorder is also improved. It is often seen in red and green blindness. For those who have not developed in the family, if the color vision disorder is detected, the visual acuity should be followed up. Early LHON is retinal involvement, followed by optic neuropathy, called neuroretinopathy. VEP examination helps to understand the status of visual function and has special diagnostic value for subclinical or occult cases.
1. Dominant optic atrophy (dominant optic atrophy) is relatively rare, is a kind of optic nerve loss of abiotrophy (abiotrophy). Most of them occurred before the age of 10, most of them had moderate vision in both eyes from 4 to 6 years old. About 40% of patients had visual acuity of 0.3 or more, and only 15% had visual impairment, which was less than 0.1. According to statistics, there is no visual loss to manual and light perception.
The outer eye and the anterior segment of the eye are normal. The fundus is characterized by a slight paleness on the temporal side of the optic disc, and a small number of severe visual impairments may be associated with nystagmus. The visual field examination can be found in the center, the side center or the dumbbell type dark spot. The white field of view is normal, but because the patient has blue blindness, the blue field of view is smaller than the red field of view. Using the graphic and flash VEP check, the patient's VEP amplitude is low and the peak latency is prolonged.
2. Recessive optic atrophy (recessive optic atrophy) is more rare, mostly after birth or 3 to 4 years old, so it is also known as congenital recessive hereditary optic atrophy. More than half of the patients have a blood relationship with their parents. The patient's vision is often severely damaged or completely blind, and there is nystagmus. If you can check the field of view, you can see the field of view shrinking and the side center dark spots. The fundus shows atrophy of the optic nerve, depression and thinning of the retinal blood vessels. Therefore, sometimes it is easy to be confused with the retinal degeneration of the blanket, but ERG can be identified: the ERG of the disease is normal, and the ERG of the retinal degeneration of the blanket is extinguished.
Members of the LHON family may exhibit other neurological abnormalities such as peripheral neuropathy, headache, migraine, mental retardation, tremor, epilepsy, deafness, spinal column involvement, cerebellar ataxia, movement disorders, dystonia, bladder weakness Zheng et al, other visible cardiac conduction disorders, occurred in 11778 mutations; 3460 mutations are susceptible to pre-excitation syndrome. A demyelinating disease resembling multiple sclerosis can be seen in the LHON family. Clinically, it has been reported that symptoms and signs consistent with multiple sclerosis (MS) can be seen in the presence of optic neuropathy. Cerebrospinal fluid and magnetic resonance imaging in these patients can be found in the typical manifestations of multiple sclerosis. The population survey did not show an increase in the incidence of mtDNA mutations in patients with multiple sclerosis. It seems that the two diseases are not necessarily related. But the merger can happen. Patients with MS who have a LHON site mutation will have a worse prognosis for optic neuritis. It can be seen that some LHON with severe neurological abnormalities is called Leber syndrome. For example, optic neuropathy still has motor disorders, paralysis, mental disorders, skeletal muscle abnormalities, and acute infant encephalopathy.
Some people think that the disease is caused by changes in the retinal blood vessels and is called "telangiectasia microangiopathy". This microvascular disease can occur before the onset of the disease, so members of the family should carefully follow the fundus. Smith believes that there may be vascular dilatation of the arterioles around the optic disc in the early stage, swelling of the retinal nerve fiber layer around the optic disc and no leakage of the optic disc. In the chronic phase, the disc is gradually pale or even pale.
The diagnosis was mainly based on medical history, clinical manifestations, and mtDNA laboratory test results.
diagnosis
Currently no relevant information
complication
More development of optic atrophy, also seen acute posterior optic neuritis.
treatment
(a) treatment
There is no effective treatment for this disease so far. Because some patients can naturally recover their vision during the course of their illness, any treatment effect should be evaluated with caution. The disease is currently being considered as one of the key research targets for gene therapy.
In order to reduce the toxic damage to the optic nerve, patients should be warned to quit smoking and abstain from alcohol. Although clinical use of neurotrophic drugs, there is no positive effect. Japan currently uses vasodilators for acute casesIdebenone(idebenone) combined with vitamin B2, vitamin C, ubiquinone (Coenzyme Q10And Isopropyl unoprostone, a prostaglandin-lowering hypotonic drug, designed to shorten the time of vision recovery.
(two) prognosis
In some patients with Leber's hereditary optic neuropathy, vision may be partially or even restored after months or even years of vision loss. Cases in which part or all of this vision was restored were statistically 29% and 12%, respectively. Once vision is restored, it usually rarely diminishes.
prevention
Smoking cessation and alcohol withdrawal may be effective. For female patients who have been confirmed as female carriers, prenatal examination should be conducted to benefit eugenics.
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