Amavrotichesky idiocy — the concept uniting group of genetically determined diseases caused by a dismetabolizm of gangliozid with their accumulation in cerebral cages. The leading symptoms of pathology are progressive decrease in intelligence and loss of sight. Diagnostic actions include neurologic survey, an oftalmoskopiya, cerebral MRT, genetic consultation, a research of lipidic composition of blood, the histochemical analysis of a brain bioptat. Treatment is symptomatic: anticonvulsive, psychotropic pharmaceuticals, transfusions of freshly frozen plasma.
For the first time the amavrotichesky idiocy was described in 1881 by Warren Tey — the ophthalmologist from the USA studying changes of an eye bottom of patients. In 1887 the neurologist Bernard Saks submitted the detailed description of a clinical picture of a disease. In the subsequent he carried out series of observations of similar cases and drew a conclusion on the family nature of pathology. The most known amavrotichesky idiocy — a disease Teja-Saks was so open. Then researchers in the field of pediatrics and neurology described other options of a disease having later debut. Prevalence of pathology in the general population makes 1 case on 500 000 population, among Jewish people — on 6 000 population. Gender distinctions in incidence are absent.
Reasons of an amavrotichesky idiocy
The family nature of a disease is caused by the gene mutations inherited on the autosomno-recessive mechanism with a high penetrantnost of a defective gene. The Amavrotichesky idiocy develops at inheritance of a pathological gene from both parents. The probability of the birth of the sick child at heterozygotic carriers of defect makes 25%. The genetic substratum of a disease Teja-Saks representing variable mutations of a gene of HEXA located on the 15th chromosome in q23-q24 locus is most studied. The specified gene codes the enzyme which is responsible for catabolic reactions with splitting of gangliozid. Fermental insufficiency leads to accumulation of gangliozid in gangliozny cells of a brain and a retina that is followed by their degeneration.
The Amavrotichesky idiocy arises owing to metabolic violations with adjournment of lipids in cerebral and retinalny cages, to a lesser extent in somatic bodies (a liver, a spleen). At an idiocy Teja-Saks as a result of violations in HEXA gene which is responsible for synthesis of lizosomny enzyme of a geksozaminidaza And, is not carried out a catabolism of GM2 of gangliozid, there is their gradual accumulation. Other forms of a disease are followed by similar dismetabolichesky shifts. In cerebral neurons and cells of a retina lipidic inclusions, various on the structure, accumulate. The infantile form differs in fine-grained inclusions with the content of cholesterol, at late children's and juvenile options of a disease the accumulation product along with lipids has a large amount of protein, cholesterol is absent.
Macroscopically amavrotichesky idiocy is shown by increase in volume of a brain, extensive atrophic changes of occipital shares, a cerebellum, thinning of visual paths. The microscopic picture in a brain is presented by swelling of gangliozny cages and their shoots, filling of intracellular space with lipoidny inclusions, wrinkling of kernels, disintegration of tigroidny substance. Similar changes are noted in retinalny cages, are most expressed in the field of a yellow spot.
The Amavrotichesky idiocy includes several clinical options differing in age of a demonstration of symptomatology, character of a current, life expectancy of patients. Possibly, they are caused by various genetic defects determined by features of metabolic violations. Specification of a clinical form of pathology is necessary for understanding of the forecast of a disease, the choice of optimum medical tactics. According to clinical features allocate four main forms:
- Early nursery (infantile form Teja-Saks). The most studied disease option. The demonstration in 4-6 months is characteristic. The current fast-progressing a lethal outcome is observed to 3-year age.
- Late nursery (Yansky-Bilshovsky's form). The debut is the share of age 3-4 years. The clinic is identical to an early children's form, has a little slowed down current. Duration of a disease makes 4-6 years.
- Youthful (Shpilmeyera-Vogt's form). Begins in 6-9 years, differs in rather slow progressing of symptoms. Patients live up to 20 years.
- Late (Kufs's form). Demonstrates in the pubertatny period or at advanced age. Has the optimum slowed-down current. The lethal outcome comes on average 10-15 years later from the moment of a symptomatology debut.
The congenital amavrotichesky idiocy which received the name Norman-Wood's form is in some cases observed. Symptoms arise in the first weeks of life of the child, the main manifestation — the termination of psychological development. Some authors suggest to bring Norman-Wood's option in classification as a separate nosology.
Symptoms of an amavrotichesky idiocy
The basis of a clinical picture is made by the progressing visual frustration, gradual loss of the acquired mental abilities. The accompanying manifestations are deafness, a convulsive syndrome, extrapyramidal violations, a cerebellar ataxy. Weight of symptomatology depends on a disease form.
The early children's amavrotichesky idiocy demonstrates decrease in physical activity of the child, loss of ability to sit, hold a head. In the subsequent fading of motive and static functions up to tetraparesis with a full obezdvizhennost continues. In an initial stage the giperakuziya which is expressed start of the child at sound irritation is typical. Violations of sight result in lack of tracking toys, fixing of a look on brilliant objects. In short terms there comes the total blindness (). Spasms with prevalence of a tonic component are noted. The bulbarny syndrome, vegetative frustration is possible (, , a hypothermia, lability of pulse). The muscular hypotonia progressing in a terminal stage to a detserebratsionny rigidnost comes to light.
The Amavrotichesky idiocy of Yansky-Bilshovsky arises on the fourth year of life. At the initial stage along with decrease in sight and cognitive violations cerebellar frustration are noted: unsteadiness of gait, rough diskoordination, . Gradually the patient loses ability to go, stand, sit. The intellectual sphere degrades to idiocy level, develops . The youthful form differs in softer current: the intelligence seldom degrades to an idiocy, visual dysfunction does not reach an amavroz, the motive sphere remains to more safe. Extrapyramidal frustration (, a trochee, a tremor), cerebellar dysfunction are typical. Deafness, emergence of epileptic attacks is possible. In some cases miksedematozny obesity is found.
The Amavrotichesky idiocy of Kufs is observed extremely seldom, proceeds without the expressed motive, visual, intellectual frustration. Demonstrates changes of the personality, restriction of a focus of interest lowered by activity. Over time there is an intellectual decrease which is seldom reaching the level of the expressed organic dementia. Various mental disorders are typical: hallucinations, nonsense, catatonia, affective psychoses. Extrapyramidal, cerebellar symptoms, epileptic paroxysms, relative deafness are possible.
At the initial stages of a disease motive and visual violations cause a frequent travmatization of the child. Sharp reduction of physical activity provokes development of stagnant pneumonia. A complication of a convulsive syndrome is the epileptic status. The dysphagy at a bulbarny syndrome is dangerous by hit of liquid and food in airways with developing of aspiration pneumonia. A number of complications is connected with adjournment of lipids in internals. Fatty dystrophy of a liver leads to development of a liver failure, fatty deposits on shutters of valves — to heart failure. Patients perish from heart, respiratory, polyorgan failure, interkurrentny infections.
The characteristic combination of a triad of symptoms (cognitive degradation, sharp deterioration in sight, motive violations) allows to assume the clinical diagnosis. Difficulties arise when determining a late form. Confirmation of the diagnosis perhaps after carrying out a number of researches:
- Survey of the neurologist. Data of the neurologic status depend on a form and the period of a disease, age of the patient. Sharp discrepancy of intellectual development to age is noted. Spastic paresis, cerebellar dysfunction, giperkineza, muscular dystonia, vegetative and trophic violations come to light.
- Consultation of the ophthalmologist. At babies lack of reaction of tracking is observed, at patients of advanced age the vizometriya confirms sharp decrease in visual acuity. Oftalmoskopiya diagnoses a bilateral atrophy of an optic nerve. The Patognomonichny sign is existence in a makulyarny zone of a cherry speck. The late amavrotichesky idiocy differs in lack of this symptom, a picture of a pigmentary retinit at an eye bottom.
- Laboratory analyses. In blood vakuolizirovanny lymphocytes are found. When conducting biochemical blood test changes of a lipidic profile (increase in level of phospholipids, cholesterol), the increased concentration of separate enzymes can be defined.
- Brain MRT. Visualizes the atrophy of cerebral fabrics more noticeable in a cerebellum, occipital area. Expressiveness of atrophic changes is maximum at an early debut, is minimum at a late form. Along with an atrophy thinning of optic nerves comes to light.
- Cerebral biopsy. The histochemical and cytologic research of material from atrophic sites allows to establish authentically the diagnosis "an amavrotichesky idiocy" on existence of characteristic intracellular lipidic inclusions. On color of coloring of inclusions it is possible to judge a disease form.
- Consultation of the geneticist. Includes collecting the family anamnesis and drawing up a family tree. Gives the chance to confirm family character, to specify type of inheritance of pathology.
The Amavrotichesky idiocy is differentiated from other hereditary dismetabolichesky and degenerate diseases with defeat of TsNS. The early children's option needs to be distinguished from a disease of Nimanna-Pika proceeding with the expressed defeat of somatic bodies. The late form demands a differentiation from a number of diseases with the leading cerebellar and extrapyramidal symptomatology (multiple sclerosis, Lafora's disease, a leykodistrofiya).
Treatment of an amavrotichesky idiocy
Specific therapy is not developed. The symptomatic supporting treatment is carried out. In the presence of epileptic paroxysms antikonvulsant, mental deviations — psychotropic drugs apply (sedative, tranquilizers, neuroleptics). Certain clinical physicians point to efficiency of transfusion of plasma, blood medicines. Vitamin therapy, the all-strengthening actions is recommended. At late stages of the patient needs careful leaving, prevention of infectious complications. The perspective direction in search of effective methods of treatment is genetic engineering, however essential results in this area are not achieved yet.
Forecast and prevention
The Amavrotichesky idiocy comes to the end with a lethal outcome. Longevity of patients depends on age of a debut of pathological changes. The infantile form has the most adverse forecast — patients perish 1,5-2 later. The slowest good-quality current is observed at late option. Preventive measures are directed to an exception of related marriages. The parents having the sick child are recommended to refuse a further child-bearing. In case of pregnancy of heterozygotic couple the concentration research geksozaminidazy-A in amniotic liquid is possible. Considerable decrease is the indication to termination of pregnancy.