Periventricular leukodystrophy. Forms, symptoms and treatment of leukodystrophy Signs of leukodystrophy

The main type of inheritance of Leukodystrophy is autosomal recessive, possibly sex-linked recessive inheritance. Along with sporadic cases, family cases are often described, in some families only boys are sick. There are cases of consanguinity between the parents of patients. Parents of patients with Leukodystrophy are phenotypically healthy.

The pathogenesis of Leukodystrophy is based on a genetically determined enzymatic defect that causes a violation of myelogenesis and the exchange of abnormally constructed myelin; initially, myelin synthesis is impaired (dysmyelination).

These diseases are characterized by brain atrophy, often with foci of softening of various ages. A common pathomorphological feature of Leukodystrophy is an extensive, relatively symmetrical dystrophic lesion of the white matter of both hemispheres of the brain, cerebellum, and spinal cord. The myelin sheaths are affected primarily and the greatest changes are, often, but to a lesser extent, the axial cylinders. Histological examination reveals multiple merging foci of demyelination of pyramidal, extrapyramidal, cerebellar pathways and associative fibers. Demyelination can be associated with spongiosis. In the white matter, a biochemical study reveals a decrease in lipids. Products of fine-grained decomposition of myelin - lipids are deposited inside and outside the nerve cells of different parts of the central nervous system, reactive hyperplasia of the gliosis tissue is revealed with the formation of gliosis scars. Lipids accumulate during internal organs, mainly in the kidneys and liver.

To a lesser extent than white matter, gray matter suffers, in which areas of death and degeneration of nerve cells are found. To one degree or another, peripheral nerve fibers are involved in the pathological process. Unlike leukoencephalitis (see the complete body of knowledge), leukodystrophy does not have inflammatory infiltrates.

Most often, Leukodystrophies begin in the early childhood, less often in youth, sometimes there are cases of the disease in adults. Children usually develop normally before illness. Its first manifestation may be a change in the child's behavior - he becomes lethargic, tearful, loses interest in his surroundings, at times heightened excitability is noted. Focal disorders soon appear and develop rapidly nervous system according to her multiple defeat. Clinical, the picture of Leukodystrophy is characterized by a wide variety of symptoms. Most patients have a variety of movement disorders - spastic, flaccid paresis, paralysis (see the complete body of knowledge Paralysis, paresis), ataxia (see the complete body of knowledge), coordination disorders, intentional tremors (see the complete body of knowledge), nystagmus (see the complete body of knowledge) ), epileptic seizures - general and Jacksonian (see full body of knowledge Epilepsy, Jacksonian epilepsy), extrapyramidal disorders - Parkinson's syndrome (see full body of knowledge), hyperkinesis (see full body of knowledge) and often myoclonic twitching in different muscle groups, including the tongue. One of characteristic symptoms is partial or complete nipple atrophy optic nerve (see complete body of knowledge), usually accompanied by loss of vision; hearing is impaired, dementia increases. A variety of vegetative disorders, hyperthermia attacks are observed. In the terminal stage of the disease, decerebrational rigidity occurs (see the complete body of knowledge), bulbar disorders. Patients die at different times from the onset of the disease ( for the most part after a few months), being in a state of cachexia, most often from aspiration pneumonia and other intercurrent diseases, sometimes during status epilepticus.

With Leukodystrophy in the blood, urine, cerebrospinal fluid, pronounced biochemical changes are found, of which the change in the content of lipids and amino acids is especially important.

In the biopsy material of the cutaneous nerves, myelin breakdown is possible.

With electroencephalography (see the complete body of knowledge), pronounced nonspecific changes are revealed - the absence or disorganization of the alpha rhythm, the presence of theta and delta waves. With electromyography (see the complete body of knowledge), a slowdown in the speed of impulses along the nerve trunks is noted.

Leukodystrophies are sometimes combined with other hereditary diseases, phenylketonuria, amaurotic idiocy.

The diagnosis is very difficult, especially in the early stages of the disease, and is often made only on sections. The question of the possibility of Leukodystrophy arises in cases of a multifocal progressive lesion of the central nervous system in a child in the presence of a patient with this disease in the family.

In the diagnosis of Leukodystrophy, a comprehensive examination of the patient is necessary, including biochemical and morphological examination of blood, urine, cerebrospinal fluid, and a study of biopsy material of cutaneous nerves.

Treatment is symptomatic. Prescribe blood and plasma transfusions, tissue extracts, anticonvulsants, dehydration agents, vitamin therapy. With Hallerworden-Spatz disease, a noticeable improvement is given by the use of a-DOPA.

If there are patients with Leukodystrophy in the family, it is recommended to refrain from childbirth. In some cases, intrauterine diagnostics by means of amniocentesis is used (see the complete body of knowledge).

Depending on the age at which the disease began, neurological symptoms, data of biochemical and pathological studies, several nosological forms of Leukodystrophy are distinguished, of which the Greenfield-Scholz metachromatic Leukodystrophy, globoid cell Leukodystrophy (Krabbe's disease), Sudanophilic Leukodystrophy ), Hallerwarden-Spatz disease.

Separate forms of leukodystrophies. Greenfield-Scholz metachromatic leukodystrophy (synonyms for late infantile leukodystrophy). This disease was described by W. Scholz in 1925 and Y. G. Greenfield in 1933. It is inherited in an autosomal recessive manner. The pathogenesis is based on a congenital deficiency in the activity of the enzyme cerebroside sulfatase (arylsulfatase A), which leads to progressive extensive demyelination and spongy degeneration of the brain tissue and to the deposition of metabolic products - sulfatides in nerve cells in the form of granules, nerve fibers, glia of different parts of the central nervous system, mainly subcortical nodes, as well as in peripheral nerves, retina, kidney tubules, blood leukocytes.

In the brain tissue, the lipid content is reduced and the sulfatide level is relatively increased. When laboratory research there is a sharp decrease or absence of arylsulfatase in leukocytes, an increase in the excretion of sulfatides in the urine.

Characteristic morphological feature Greenfield-Scholz disease consists in the fact that during histological examination sulfatide granules turn brown, although the dye blue toluidine is used (the phenomenon of metachromasia); with the Austin test, which is important for the diagnosis of metachromatic leukodystrophy, the patient's urine sediment turns brown when blue toluidine is added.

The disease most often begins at the age of 1-3 years, although there are cases of earlier and later onset. The first symptoms of the disease are atactic disorders, muscle atony with a decrease in tendon reflexes. In the future, spastic paresis, paralysis, epileptic seizures appear, dementia increases, decerebral rigidity, cachexia develops.

Sometimes the disease manifests itself in the form of polyneuropathy (see the complete body of knowledge Polyneuritis) without symptoms of damage to the central nervous system. In these cases, for the purpose of diagnosis, biopsy material of the cutaneous nerves is examined, in which myelin breakdown and metachromatic granules are found.

The life expectancy of most patients is from several months to 1 year, sometimes up to 10 years or more. Depending on the age at which the disease begins, congenital, childhood, adolescent and adult form metachromatic L

Globoid cell leukodystrophy was described by KN Krabbe in 1916; named for the author (Krabbe's disease).

The disease is transmitted in an autosomal recessive and sex-linked recessive manner. Only boys are ill.

The pathogenesis is associated with a deficiency or absence of β-galactosidase, which causes a violation of the metabolism of cerebrosides.

Malone (N. I. Malone) et al (1975) investigated the content of p-galactosidase in members of one family. It was absent in children with Krabbe's disease, and in their parents - phenotypically healthy heterozygotes for the gene for this disease - its activity was reduced compared to the control group. This observation is of interest from the point of view of identifying heterozygosity. Autopsy reveals significant atrophy of the brain with areas of compaction in the subcortical white matter due to astrocytic gliosis. Microscopic examination reveals, along with widespread demyelination, foci of spongy dystrophy, mainly in the upper layers of the cerebral cortex and in the U-shaped associative fibers. Histopathological features of Krabbe's disease are large single and multinucleated globoid (spherical) cells of adventitious histiocytic origin.

The disease begins in the first months after birth, in some cases a later onset was noted (at 3-6 years of age). The first clinical manifestations of the disease are expressed by frequent short-term bouts of stiffness with opistotoius (see the complete body of knowledge), atrophy of the discs (nipples) of the optic nerves with loss of vision is rapidly developing, epileptic seizures are observed, myoclonus in different muscle groups, swallowing is impaired, dementia develops, which can reach the degree of idiocy, in the terminal stage decerebral rigidity arises. Patients usually die several months after the onset of the disease during status epilepticus or from aspiration pneumonia.

Sudanophilic leukodystrophy was described by F. Pelizaeus in 1885, L. Merzbacher

in 1908; named after the authors (Peliceus-Merzbacher disease). The type of inheritance of the disease is autosomal recessive. Both sexes get sick equally often. There are indications of the possibility of dominant inheritance. A histological examination of the brain reveals, along with sparse myelin fibers, many completely preserved ones. A characteristic histopathological sign of Peliceus-Merzbacher disease is the red staining of perivascular deposits of disintegrated myelin in different parts of the brain by Sudan III. A biochemical study shows a decrease in cholesterol, sphingomyelin, and cerebrosides in the brain tissue.

The disease begins in different ages, more often in the chest, sometimes it can be congenital. Its first symptoms are ataxia, nystagmus, head tremors, intentional tremors, chanted speech, strabismus. In the future, join central paresis, paralysis of the extremities, atrophy of the nipples of the optic nerves, often only the temporal halves, in most cases, intellectual impairment is mild.

Peliceus-Merzbacher disease has the most favorable course in comparison with other Leukodystrophies. Patients can live for decades, the process develops slowly, remissions are possible.

Hallerworden-Spatz disease (synonyms for progressive rigidity). In 1922, Hallervorden and Spatz (J. Hallervorden, N. Spatz) described a family in which there were 5 patients with this disease. The type of inheritance is autosomal recessive. Pathological changes in Hallerworden-Spatz disease are most pronounced in the subcortical nodes. Their feature is an increased amount of iron-containing pigment in the pallidus and black matter of the brain, due to which these formations have a brown color. In hyperplastic gliosis tissue, cells with a large nucleus are found, resembling Alzheimer's glia. Biochemical examination of brain tissue reveals a violation of the metabolism of lipids, iron, catecholamines.

The disease often begins at the age of 9-10, but adults also get sick. In the clinical picture of the disease, the main place is occupied by extrapyramidal movement disorders. The first symptoms are hyperkinesis of an athetosis, torsion-dystonic nature, akinetic-rigid syndrome (see the complete body of knowledge Tremor paralysis), in some cases atactic disorders join. Changes in the emotional and intellectual sphere of varying severity can be observed, mostly moderate. The course of the disease is slowly progressive.

Spongy degeneration of white matter (synonyms: Canavan disease, Canavan-Van Bogart-Bertrand disease).

The type of inheritance is autosomal recessive and recessive, sex-linked: almost exclusively boys are affected. The disease occurs in utero and clinically manifests itself in the first days after birth. Pathological examination reveals swelling of the brain tissue, spongiosis and demyelination of the white matter of the brain with a decrease in cerebrosides and sphingomyelin.

Epileptic seizures are often the first symptoms of the disease; the child is lethargic, drowsy, dementia develops rapidly, paresis of the legs appears nystagmus, strabismus, hearing loss, as well as vision due to atrophy of the optic nerve discs, swallowing is upset.

The course of the disease is rapidly progressing, in the terminal stage, decerebral rigidity is observed.

Life expectancy does not exceed two years. Patients die during status epilepticus or from intercurrent illness.

Leukodystrophy with diffuse Rosenthal fibrous formation (Alexander's disease) is very rare.

A pathological examination of the central nervous system reveals an enlargement of the brain, widespread demyelination with focal softening of various sizes, especially the accumulation of hyaline described by S. Rosenthal.

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Leukodystrophy Krabbe is a hereditary disease, one of the most severe genetic pathologies, which is based on the destruction of melanin, a substance that covers the brain, nerve trunks and endings. In this case, the decay of the shell is progressive and irreversible.

The incidence is one case per 100 thousand newborns born alive. The disease is caused by a mutation that occurs on chromosome 14, more precisely, in one of the genes that are located in it.

Causes and risk factors

This pathology mainly develops in boys. In 85% of all cases, it manifests itself when a child is born from closely related marriages. But there is also such an option when the parents are carriers of the defective gene, but they do not manifest this in any way.

In this case, with a probability of 50%, the child is born with leukodystrophy. Therefore, any family that has already encountered the manifestations of this disease should receive medical genetic counseling during the planning period.

You can also do a test to determine the defective gene during pregnancy. In this case, with a positive result, the question of termination of pregnancy may arise.

Symptoms

Krabbe leukodystrophy begins to manifest itself with early age... The first signs become noticeable at the age of 3 to 6 months, with the first and most important symptom being elevated temperature body that is not called by any inflammatory diseases... Often, doctors cannot understand why hyperthermia is motivated, therefore treatment long time is carried out completely inadequate.

Other symptoms that appear literally within the first two months include hyperexcitability, malnutrition, rigidity of the arms and legs, convulsions, and vomiting. Gradually, parents begin to notice that the child is lagging behind in his development, both physical and mental.

Despite the fact that each form of leukodystrophy has its own symptoms, and Krabbe's disease is one such form, all diseases of this type have characteristic signs.

In the first few months of life, babies seem completely healthy. Moreover, Krabbe's disease can develop not only in babies under one year old, but also in adolescence, and even in adulthood. In this case, it is not so acute, progresses more slowly, but still ends in death, since they have not yet learned how to treat such genetic pathologies.

The second clear sign is a violation of motor activity. This occurs due to the destruction of myelin not only in the brain, but also in the nerve endings that cause movement. At first, muscle tone is significantly reduced, after which the limbs practically stop moving. Some time after the onset of the disease, the child completely forgets all the previously mastered skills - he ceases to sit, roll over from side to side or on his back, and walk.

All this is accompanied by cramps and muscle twitching. As the pathology progresses, and this happens quite quickly, for which parents must be prepared, a complete loss of brain function will occur.

All symptoms can be divided into three stages. The first develops up to six months of age, the second - at the age of 6 - 8 months, and then the third stage sets in, in which such body functions as swallowing, vision, hearing are lost. Also, any motor functions are completely absent.

Diagnostics

1. Study of complaints and dynamics of the development of the disease.
2. Family history examination.
3. General inspection.
4. CSF analysis.
5. CT or MRI of the brain.
6. Molecular genetic research.

It is also possible to diagnose the fetus before birth. For this, amniotic fluid is taken for research.

Treatment

There is no cure for Krabbe leukodystrophy. In the early stages of the disease, while it is just beginning to manifest itself, it is possible to use bone marrow transplantation or the introduction of umbilical cord blood in the treatment. However, it can only help if the disease is just beginning to develop. But often the diagnosis is made when the child practically stops moving. In this case, both of these methods will be completely useless.

The prognosis is always unfavorable. It is very rare for children to live up to the age of two. But if the disease begins to manifest itself at a later age, then it does not progress so quickly and life expectancy is 4 - 7 years.

Leukodystrophies - a group of severe hereditary metabolic diseases characterized by damage to the white matter of the brain. With leukodystrophies, metabolism is impaired myelin, that is, a substance that forms the sheath of the nerve processes and ensures effective transmission of signals in the nervous system (it is myelin that gives the white matter of the brain its color).

Myelin is made up of a number of different components and therefore depends on many genes for its function. A defect in one of these genes can interfere with myelin sheath formation or maintenance. The transmission of nerve signals is dramatically slowed down, motor and intellectual disorders occur, and the perception of signals from the sense organs worsens. With further destruction of myelin, these disorders intensify, over the course of several years leading to profound physical and mental degradation and then to the death of the patient. is still the only method to stop or slow down the development of the disease in some patients.

Leukodystrophies are a group of rare diseases that differ in their nature and frequency of occurrence. Here are some of them:

• Adrenoleukodystrophy... A special type of substance accumulates in tissues - fatty acids with very long chains, since their breakdown in this disease is impaired. As a result, the structure and function of myelin is impaired.
• Metachromatic leukodystrophy caused by a deficiency of the enzyme arylsulfatase A. The body accumulates sulfatides - substances that have a destructive effect on myelin.
• Globoid cell leukodystrophy, or Krabbe's disease, is associated with a violation of the production of the enzyme galactocerebrosidase. This leads to the accumulation of substances that have a toxic effect on the myelin sheaths.

There are also several other very rare leukodystrophies.

With many leukodystrophies, several forms of the disease are distinguished, depending on the age at which the first symptoms appear. This is important for predicting the development of the disease (as a rule, the earlier the symptoms appear, the faster the disease progresses) and for planning bone marrow transplantation, if possible. So, for adrenoleukodystrophy, a typical childhood form with the onset of symptoms at 4-10 years old and several other forms, including adrenomyelopathy, which is typical for adulthood and is not so difficult. For metachromatic leukodystrophy, there are late infantile (onset of symptoms in 1-2 years), juvenile (in 3-10 years) and adult (after 16 years) forms. Infantile (from 3-6 months), late infantile (from 6-18 months), juvenile and adult forms are known for globoid cell leukodystrophy.

Frequency of occurrence and risk factors

Leukodystrophies are rare diseases. So, adrenoleukodystrophy occurs with a frequency of approximately 1 in 40 thousand newborn boys. Metachromatic leukodystrophy has a frequency of about 1 in 50-70 thousand newborns, globoid cell leukodystrophy - about 1 in 100 thousand. Some types of leukodystrophies are so rare that only a few hundred cases have been described worldwide.

Leukodystrophies are genetically determined diseases, and the type of inheritance depends on the specific type of leukodystrophy. Most leukodystrophies (including metachromatic and globoid cell) are inherited in an autosomal recessive manner, that is, the probability of a child's illness is 25% if both parents are carriers of the disease. These diseases affect boys and girls with the same frequency. They occur more often in communities where closely related marriages are common, and can occur with different frequencies in different nations.

Adrenoleukodystrophy is usually characterized by X-linked inheritance and, therefore, in most cases occurs in boys - if the mother is a carrier of the disease, the probability of the disease in her son is 50%.

Families who have already had cases of the birth of children with any type of leukodystrophy are advised to consult a geneticist before the birth of all subsequent children.

Signs and symptoms

At birth, children with leukodystrophy usually appear healthy and develop over time according to age. However, then symptoms of damage to the central nervous system gradually appear. These symptoms vary somewhat depending on the specific disease and its form, but still have common features.

Movement disorders are common. In children, coordination of movements deteriorates, problems with balance are noted, it becomes difficult to walk and run. Possible muscle weakness, abnormally increased or decreased muscle tone, muscle twitching. Convulsive seizures appear. Behavior changes occur. Memory and intelligence gradually decline. Vision and hearing deteriorate. The child gradually "rolls back" in his development, losing the previously acquired motor and intellectual skills. In the later stages of the development of the disease, blindness, deafness, paralysis, and the inability to swallow food normally occur. As a rule, the earlier the signs of the disease appear, the faster it progresses.

There are also symptoms characteristic of specific types of leukodystrophy. So, with adrenoleukodystrophy, in addition to disorders from the central nervous system, signs of adrenal gland damage are also revealed.

Diagnostics

The lesion of the white matter of the brain, characteristic of leukodystrophies, is detected by means of magnetic resonance imaging (MRI). As a rule, abnormalities on MRI associated with the destruction of myelin are visible long before the onset of clinical symptoms, and subsequently the degree of these abnormalities corresponds to the severity of the patient's condition. With many leukodystrophies in the cerebrospinal fluid, high level squirrel.

To clarify the type of leukodystrophy, biochemical tests can be used - measuring the levels of enzymes whose synthesis or transport is impaired in a particular disease, or detecting those substances that accumulate in this disease. Other studies are also possible, including molecular genetic studies.

For some types of leukodystrophy (including metachromatic, globoid cell and adrenoleukodystrophy), prenatal diagnostic methods have been developed.

Treatment

In fact, the only treatment for leukodystrophies today is allogeneic bone marrow (or cord blood) transplantation from a healthy donor. If successful, it can lead to the normalization of the level of missing protein, which means an increase in the duration and quality of life. Thus, there are known cases of the use of transplants for the treatment of adrenoleukodystrophy, metachromatic leukodystrophy and globoid cell leukodystrophy.

At the same time, the use of transplants for leukodystrophies is associated with serious limitations. It is very important to carry out the transplant as early as possible, before the development of noticeable neurological disorders. Indeed, transplantation does not allow "fixing" the already existing lesions of the central nervous system, but only stops or slows down their further progression. But it is also necessary to take into account the rate of development of neurological lesions.

So, with the most rapidly developing forms of leukodystrophies, it is often impossible to avoid death or severe disability of the patient even after transplantation. This is due to the fact that after transplantation, it takes some time (for example, with some leukodystrophies, it can be 12 or even 24 months) before the work of donor cells will lead to the normal functioning of myelin. And all this time, the development of the disease will continue. Therefore, in forms with a very early onset of the disease, hopes are mainly associated with those transplants that were carried out before the onset of clinical symptoms (for example, if leukodystrophy was already found in the older child in the family and therefore the youngest child underwent early diagnosis). With a slower progression of the disease, the chances of success increase.

If bone marrow transplantation is not possible or not recommended, then palliative therapy remains to relieve symptoms of the disease. New treatment approaches are constantly being developed, but so far they remain experimental.

It is believed that it is possible to slightly slow down the development of adrenoleukodystrophy (including pending transplantation) with the help of a special diet. Sometimes Lorenzo oil is also used - a remedy developed by the parents of a boy with adrenoleukodystrophy. However, it is still unclear how effective this remedy is.

Forecast

The prognosis for leukodystrophy is generally poor, especially for early-onset and rapidly worsening forms of the disease. However, allogeneic transplantation of bone marrow or cord blood can help some patients. If successful, it stops or slows down the progression of the disease, allows in many respects to preserve motor and intellectual functions. In this case, the most important condition is timely transplantation.

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Metachromatic leukodystrophy... This type of leukodystrophy belongs to the most common type of white matter degeneration of the brain in children. It is inherited in an autosomal recessive manner. In this disease, the deficiency of the enzyme arylsulfatase A in the brain and other tissues is determined. Normally, when exposed to this enzyme, a sulfate group is cleaved from ceramide galactose sulfate, or sulfatide, which is a normal component of myelin lipids. A large amount of sulfatide accumulates in the white matter of the brain, which can be easily identified by light microscopy by metachromatic staining (reddish brown) with toluidine blue. Similar accumulations of sulfatide are found in peripheral nerves. Diffuse demyelination, spreading to all parts of the nervous system, is especially pronounced in areas whose myelination occurs later.
Clinical signs usually appear at the age of about a year, but can also appear at an older age. Initially, the child has a disturbed gait, and he cannot learn to run and walk up stairs. IN early stage diseases are marked by spasticity of the extremities, hyperreflexia and the extensor plantar reflex. All tendon reflexes are alive, with the exception of the knee, which is reduced or absent due to damage to peripheral nerves. In the case of their severe damage, paresis and atrophy of the distal muscles, especially the legs, occur. Eventually the child is bedridden mental development his backward. Death usually occurs before reaching the age of 10 years. With a late onset, the main signs are extrapyramidal movement disorders and mental retardation.
The final diagnosis depends on the absence or significant decrease in the activity of sulfatase A in one tissue of the body or several. Most suitable for determining the activity of the enzyme are renal tubular cells obtained from urine sediment, leukocytes or a culture of fibroblasts. Rapid, but insufficiently accurate, methods include the determination of metachromatic material in urine sediment stained with toluidine blue. Dysfunction of the gallbladder with the accumulation of sulfatides on its walls can be determined by a filling defect detected by oral cholecystography. Conduction is impaired in peripheral motor and sensory nerves. CSF protein levels are usually elevated, which is a valuable diagnostic feature in differentiating leukodystrophy from a large group of non-progressive movement disorders related to cerebral palsy. Differentiation is essential in terms of genetic counseling and prognosis. Metachromatic leukodystrophy in the fetus is diagnosed based on the activity of arylsulfatase in cell culture amniotic fluid; the study is offered to future parents if they have pathologically altered genes.
Krabbe's disease(cerebroside lipidosis or spherical leukodystrophy). The disease is inherited in an autosomal recessive manner. Pathological signs with it are the diffuse absence of myelin in the white matter of the brain and the accumulation of specific, giant multinucleated cells (spherical cells). It has an increased ratio of cerebroside (ceramide galactose) to sulfatide (ceramide galactose sulfate) against the background of an unchanged absolute amount of cerebroside. These changes are considered secondary to the lack of galactocerebrosidase activity.
The disease is detected at an early age, when the child develops progressive rigidity, hyperreflexia, the swallowing process is impaired, and his physical and mental development lags behind. Involvement of peripheral nerves in the process leads to muscle hypotension; the child dies in the first 2 years of life. The diagnosis is made by determining the activity of galactocerebrosidase in peripheral blood leukocytes. The level of protein in the CSF is increased, the conduction along the peripheral nerves is reduced. Prenatal diagnosis is possible by determining the activity of enzymes in the amniotic fluid cell culture.
Adrenoleukodystrophy... The disease is inherited in a recessive manner, linked to the X chromosome. Pathological signs are reduced to degeneration of the white matter with the accumulation of myelin breakdown products, mainly neutral fats. In the macrophages of the affected tissues, typical zigzag inclusions are revealed. In the atrophied adrenal cortex, cells contain similar inclusions.
At the heart of the disease is a violation of the metabolism of hexacosanoate - a long-chain fatty acid C26 - accumulating in the brain matter, adrenal glands, muscles, plasma and fibroblast culture. Plasma research helps to clarify the diagnosis and identify carriers of the gene.
The disease usually begins by the end of the first 10 years of life and is manifested by progressive spasticity, dementia, and at a later date - skin pigmentation and other signs of Addison's disease. In some cases, the process involves mainly the spinal cord and peripheral nerves (adrenomyeloneuropathy). A variant of the disease with onset in early childhood is described.
Some forms of leukodystrophies are still not fully defined and are usually diagnosed only with sectional examination of the brain.
Canavan's disease (spongy degeneration of the white matter of the brain). The disease is inherited in an autosomal recessive manner. When histological examination The brain exhibits a characteristic diffuse vacuolization of cells in the deep layers of the cortex and subcortical white matter, apparently as a result of excessive accumulation of water in glial cells and myelin matter. Symptoms in young children include inadequate control of head movements, blindness, optic atrophy, rigidity, hyperreflexia, and progressive macrocephaly. Based on the latter, hydrocephalus or fluid accumulation in the subdural space is suggested. However, the size of the ventricles does not change or they are slightly dilated: Death occurs within 5 years.

Peliceus-Merzbacher disease. The disease is inherited in a recessive manner, linked to the X chromosome. In children, it begins with nystagmus and head shaking, followed by ataxia, spasticity, and choreoathetosis. The disease progresses slowly and patients live to adulthood. Differentiate from cerebral palsy hard enough.

Peliceus-Merzbacher disease is essentially a group of incompletely studied demyelinating diseases, in which there is a gross, atactic disorder and abnormalities in the functioning and structure of the myelin sheath in the white matter of the brain. The disease is transmitted hereditarily, in a recessive way X-linked to the sex, therefore, only boys are sick, girls are carriers of mutated genes.

ICD code 10 G37.8. ICD 11 encryption will most likely be carried out under the code 8A44.0, in the class of diseases of the nervous system, heading demyelinating diseases, subheading leukodystrophy, or in the section on developmental anomalies, under the code LE12.

Causes

Pelizaeus-Merzbacher disease is hereditary disease... Classically transmitted by a recessive X-linked mode of inheritance (chromosome Xq22), it is caused by an abnormality in the gene encoding the synthesis of a proteolipid protein, which is structurally important for the formation of myelin in the central nervous system, as well as for the differentiation of oligodendrocytes. Mutations in the same gene can lead to the development of familial spastic paraparesis.

At present, approaches have been developed to molecular diagnostics of the disease using mutational analysis. But despite this, as in a number of other diseases with an X-linked type of inheritance, the diagnosis of Peliceus-Merzbacher disease has a number of difficulties, because mutations in exons are detected only in 10-25% of patients with this disease.

Symptoms

Pelizaeus-Merzbacher disease is characterized by a triad of symptoms: severe vertical and / or horizontal-rotator nystagmus, nodding head movements, and impaired coordination. The disease makes its debut in infancy (5-10 months) is characterized by a slow rate of progression. Gradually, an increase in muscle tone, atrophy of the optic nerve, bradilalia (slowing down of the rate of speech), a progressive decrease in intelligence are added to the above symptoms. In the later stages, symptoms of Parkinsonism, hyierkinesis join, and dementia increases. The disease progresses especially rapidly in the first years of life. In the future, periodic remissions are sometimes observed for a long time, but without significant regression of the existing symptoms.

Diagnostics

The diagnosis is based on the identification of the characteristic triad of the above neurological symptoms in infancy with their gradual slow increase. In the cerebrospinal fluid, a slight increase in protein levels can be detected, as well as cytosis. The main pathomorphological changes on the part of the nervous tissue include the absence of the myelin sheath of intact axons, which also implies a dysfunction of the oligodendroglia. Studies have shown the existence of a genetic defect in the biosynthesis of the proteolipid apoprotein, which plays a role in the differentiation of oligodendrocytes and the maintenance of their functioning. On the MRI study, a symmetrical pattern of slowing the rate of myelination is determined (see photo). Studies of the brainstem in the early stages of the disease show a pattern of absence of III-V waves. In the study of visual evoked potentials, a slowdown in latencies is noted, somatosensory evoked potentials show the absence of cortical responses, or also a slowdown in latencies. The data are of great importance when examining boys in the presence of nystagmus, allowing in most cases to make a full differential diagnosis diseases.

Treatment

There is no pathogenetic treatment for Peliceus-Merzbacher disease. They resort to general methods of rehabilitation. In some cases, symptomatic treatment is possible.

Forecast

The prognosis is poor. The disease always ends in death, more often by the second or third decade of life.

Literature sources

Mikhailova S.V., Zakharova E.Yu., Petrukhin A.S. Neurometabolic diseases in children and adolescents. Diagnostics and approaches to treatment. -M: Litterra Publishing House, 2011.-S. 324-331.

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