Contents of the article

Leukodystrophies(progressive sclerosis of the brain) - group hereditary diseases nervous system caused by disorders of myelin lipid metabolism.
Leukodystrophies are inherited in an autosomal recessive manner, with the exception of sudanophilic leukodystrophy, which is characterized by recessive, sex-linked inheritance.

An enzyme defect generated by genetic factors leads to disturbances in the course of myelination. The myelin produced by the body disintegrates. In turn, its partial or complete absence leads to defeat white matter, causing dementia. Certain forms of this disease are more common in male patients.

As a rule, the first manifestations of brain leukodystrophy overtake the patient in childhood (even before entering school). This occurs much less frequently in adolescence and adolescence. This feature characteristic of the entire group of the disease. One of the first symptoms of the disease is impaired motor function. This may be paralysis or paresis, or hyperkinesis is less common. Disorders in motor coordination and dysarthria are noted. Somewhat later, due to its progressive course, the disease can lead to convulsions in the various parts body and damage to the optic nerves.

The extensive list of symptoms includes progressive cerebellar, pyramidal and extrapyramidal disorders, decreased quality and acuity of vision and hearing, increasing dementia, and epileptiform seizures. It is extremely rare that patients also note sensory disturbances. As the disease progresses, clinical picture is supplemented by symptoms of mental degradation of the patient, spastic paresis. Terminal stage, as a rule, is characterized by decerebrate rigidity.

When conducting morphological studies, specialists discover localizations of myelin decay in the tissue of the cerebellum and brain of the patient, most often symmetrical and weakly limited, diffuse. There is a marked accumulation of myelin decomposition products in the tissues of various organs, incl. and brain.

Diagnosis of the disease is carried out based on the patient’s complaints detected clinical symptoms. Important role information obtained after conducting a diagnosis plays a role in making a diagnosis. biochemical analysis, CT and MRI of the brain. Treatment methods are also individual and depend on the diagnosis, the condition of the body and the stage of the disease. The specialist makes the decision to use one or another type of therapy based on the data obtained during the diagnostic measures.Leukodystrophies include:

• metachromatic leukodystrophy (Scholz disease),
• Pelizaeus-Merzbacher sudanophilic leukodystrophy,
• globoid cell leukodystrophy (Krabbe disease),
• individual rare and combined forms.

Metachromatic leukodystrophy

This disease was first noted by A. Alzheimer at the beginning of the last century (more precisely, in 1910). It was studied in more detail in 1925 under the guidance of neurologist Scholz. These and later scientific works allowed medicine to find out that the cause of the disease is a hereditary change in the arylsulfatase A gene, located within chromosome 22. This deviation leads to a disrupted process of converting sulfatide into galactocerebroside. As a result, excess amounts of sulfatides “drift” in the human body, accumulating within the liver and kidneys, less often affecting the lungs and heart, as well as the spleen, gastrointestinal tract, skin and bones. As a rule, the functionality of the organs does not decrease. Sulfatides harm the gallbladder, causing its pathological functioning, and also harm the performance of the central nervous system and peripheral nervous system. Accumulating in the white matter, these elements cause demyelination of the myelin sheath of the peripheral nerves.

These changes in the body are reflected in a group of symptoms that determine various stages and forms of the disease. Metachromatic leukodystrophy in its course it differs as late infantile (in four stages), juvenile and adult forms. The onset of the disease is manifested in muscle weakness and hypotension of the limbs, impaired tendon reflexes, and difficulty walking. Subsequently, the child demonstrates developmental retardation (physical and intellectual), limited movements, severe violations mental health. In most cases, the patient dies in early age, less often death occurs during the juvenile form (after 3 and up to 10 years), even less often - adult form(in the period from 40 to 50 years).

Diagnosis and treatment in each case are individual and depend on the indications received from the patient, his environment and on the basis of diagnostic measures. In general, a treatment that can prevent death has not yet been found. To alleviate the patient's condition, attempts are being made to normalize the synthesis of sulfatides.

Krabbe leukodystrophy

This form of leukodystrophy is expressed in degenerative damage to the human nervous system of a progressive nature. The defect leading to the development of the disease is inherited in an autosomal recessive manner and leads to a decrease in the concentration and activity of galactosylceramide-b-galactosidase. As a result, the process of breakdown of galactocerebroside into ceramide and galactose is disrupted or slowed down, which leads to increased concentration galactocerebroside in organs, as well as a lack of galactose and ceramide.

Free galactocerebroside accumulates in the white matter of the brain, as well as in the liver, kidneys and spleen, in leukocytes and fibroblasts. A significant (from 10 to 100 times) increase in the concentration of this substance leads to demyelization, as a result of which peripheral nerves are susceptible to axonal degeneration.

Krabbe leukodystrophy, as a rule, appears upon reaching 4 months of life. At this time, the child is very excitable and exhibits muscle hypertension. Constantly straightened limbs and clenched fists, as well as subsequent retardation in psychomotor development, indicate the disease. In the future, spastic tetraparesis, impaired tendon reflexes, and a characteristic motor reaction in the event of auditory stimuli may be observed. When examining the fundus, optic nerve atrophy may be noted. IN in rare cases peripheral neuropathy is possible. As a rule, death occurs within a period of 7 months to 3 years.

Diagnosis and decision making regarding possible method relief of the patient's condition occurs on the basis of a biochemical analysis of cerebrospinal fluid. Specific treatment of this disease absent. Diagnosis is often carried out prenatally.

Pathological anatomy of leukodystrophies

The main changes identified during a morphological study of the brain of patients who died from leukodystrophy are edema and swelling meninges, internal hydrocephalus. The cerebral cortex is sharply thinned, the white matter is dense, the convolutions of the brain are narrow, the grooves are deep. Diffuse gliosis and sclerosis of the brain, pericellular and perivascular edema are pronounced. The white matter is especially affected; the damage to nerve cells is obviously secondary. At metachromatic leukodystrophy metachromatic substances representing lipoids and sulfatide groups were found in areas of demyelination, nerve cells and in some internal organs. At globoid cell form leukodystrophy, globoid cells are detected in the brain. IN large quantities they are found in areas of significant demyelination. The origin of the cells is adventitial-histiocytic, they play the role of phagocytes. In patients with Sudanophilic leukodystrophy Pelizaeus-Merzbacher myelin damage in the brain has a patchy character, which is manifested by alternating preserved and demyelinated areas. Foci of demyelination are made of sudanophilic granular balls, many of the cells are increased in size, ugly shape, have two or more cores. Diffuse proliferation of fibrous astroglia is observed near foci of demyelination. There are a significant number of plasma cells around the vessels in the form of couplings. Foci of demyelination are located diffusely in the cerebral hemispheres, brain stem and cerebellum. The predominant localization of areas of demyelination around the vessels and the presence of sudanophilic granular balls represent the characteristic morphological features of this form of leukodystrophy. Along with this, there is a pronounced reaction of glial tissue and serious dystrophic changes nerve cells of the cortex cerebral hemispheres and subcortical nodes.

Pathogenesis of leukodystrophies

In leukodystrophies, certain lipids accumulate in various organs and fabrics. Thus, with metachromatic leukodystrophy, sulfatides accumulate in the white matter of the brain and the level of phospholipids, cholesterol, and proteolipids is reduced; in the gray matter, the lipid content was not significantly changed. With globoid cell leukodystrophy (Krabbe disease) in the white matter of the brain and spinal cord pronounced demyelination and accumulation of csrebrosides are observed with a decrease in fractions of other lipids. In sudanophilic leukodystrophy, a decrease in all lipid fractions was found, except for sphingomyelin.

Leukodystrophy Clinic

The leading symptoms in the clinical picture of leukodystrophies are neurological disorders that differ in progression. The appearance of clinical symptoms is observed mainly in the first years of life. In some cases, the onset of the disease can be observed at school and young age (juvenile form). As early signs Convulsive seizures, hyperkinesis, and spastic paresis of the limbs are often detected. As the disease progresses, other neurological symptoms may appear: strabismus, head tremors, coordination disorders, changes in muscle tone, decreased intelligence, loss of acquired speech functions, autonomic disorders. In the fundus of the eye, primary atrophy of the optic nerve nipples is detected with great constancy. IN cerebrospinal fluid protein-cell dissociation is detected.

Clinic of metachromatic leukodystrophy

Typical signs of the metachromatic form of leukodystrophy are symptoms indicating diffuse damage to the nervous system. Spastic paresis and paralysis, ataxic syndrome, pseudobulbar symptoms, progressive dementia, decreased vision and hearing, and polymorphic seizures are especially common. Characteristic autonomic disorders: swelling, decreased nutrition, hyperhidrosis or dry skin, hypersalivation. The course of the disease is progressive. In the final stage of metachromatic leukodystrophy, states of decerebrate rigidity, increased frequency of convulsive seizures, and hyperthermic crises are revealed. Fatal outcome occurs as a result of pneumonia, cardiac and respiratory failure. At laboratory research marked diffuse changes on EEG, protein-cell dissociation in the cerebrospinal fluid, often without an increase in cerebrospinal fluid pressure - ex vacuo hydrocephalus, optic nerve atrophy. Depending on the character clinical symptoms metachromatic leukodystrophy must be differentiated from childhood cerebral palsy, epilepsy, spinal amyotrophy, encephalitis. Biochemical studies that reveal specific changes in the metabolism of sulfatides contribute to clarifying the diagnosis - positive test Austin with urine - the appearance of golden-brown bodies, visible under a microscope when urine sediment is stained with toluidine blue; The Austin test is specific for the metachromatic form of leukodystrophy, as well as changes in lipids in the blood and especially in the CSF.

In the cerebrospinal fluid of patients metachromatic leukodystrophy an increase in the level of cerebrosides (due to sulfatides) is detected on average to 0.53 mg% (normally 0.24 mg%).
Since sulfatides are an important component myelin, their change can be considered as a result of a disorder in the metabolism of myelin lipids - dysmyelination.

Clinic of globoid cell leukodystrophy (Krabbe leukodystrophy)

Most malignant course The disease is observed in patients with globoid cell leukodystrophy. The disease begins in the first year of life, usually before 6 months. Patients develop convulsive seizures that are clonic-tonic in nature. Petite seizures are also noted. As the disease progresses, seizures become more frequent and prolonged. Children are lagging behind physically and mental development, lose previously acquired skills, and cease to recognize their parents. Celebrated in initial stages disease, muscle hypotonia is replaced by hypertension; in the advanced stage of globoid cell leukodystrophy, all patients exhibit spasticity and subsequently a state of decerebrate rigidity. Hyperthermic crises often occur - body temperature rises to 40-41 ° C and is maintained for several days. Some external features of the patients are noteworthy: large head, blonde hair, short neck; Various dysplastic signs are also noted. The fundus reveals partial or complete atrophy optic nerves. Gradually, patients develop cachexia. Hydrocephalus is also characteristic, bulbar disorders, organic dementia. Protein-cell dissociation increases in the cerebrospinal fluid. In the blood plasma of patients it is found sharp increase free cholesterol level exceeding normal indicators 3.5-9 times. There is also a moderate increase in individual phospholipid fractions. A study of lipids in peripheral blood erythrocytes reveals a decrease in the amount of sphingomyelin.

Pelizaeus-Merzbacher Sudanophilic Leukodystrophy Clinic

A peculiar clinical picture is observed in patients with sudanophilic leukodystrophy Pelizaeus-Merzbacher. Boys, sometimes relatives or cousins(mothers are sisters). Early neurological symptoms are nystagmus, head tremor, delayed physical and mental development. Nystagmus is detected from the birth of a child or in the first months of life; it is horizontal in nature with a rotatory component; sometimes vertical nystagmus is also observed. Head tremor is observed at rest, becoming especially pronounced when trying to hold the head. All patients have a delay in physical and mental development: children begin to hold their heads, sit, and stand late; speak and understand spoken speech poorly. In some patients, along with delayed physical and mental development, the disease debuts with progressive weakness in the limbs, seizures. In the advanced stage of sudanophilic leukodystrophy, all patients exhibit spastic paresis, impaired coordination, scanned speech, and organic dementia. Hydrocephalus, strabismus, pigmentation disorders, and degenerative stigmas are typical. The course of the disease becomes slower with age and can become stationary, which represents a certain feature of this form of leukodystrophy. At additional research detect optic nerve atrophy; in the cerebrospinal fluid - mild protein-cell dissociation. Diagnosis of the disease helps to establish the type of inheritance. The main type is recessive, sex-linked, although in some cases an autosomal recessive type of inheritance cannot be excluded. Biochemical study of lipids allows you to clarify the diagnosis. The content of sphingomyelin and glycolipids, as well as free cholesterol, moderately increases in the blood plasma. In peripheral blood erythrocytes of patients with Pelyceus-Merzbacher leukodystrophy, the content of sphingomyelin is reduced, while the level of cephalin and lecithin is slightly increased.
The content of free cholesterol increases; the level of glycolipids in erythrocytes remains virtually unchanged. These data suggest that sudanophilic leukodystrophy is characterized by a decrease in sphingomyelin in erythrocytes and its increase in blood plasma, an increase in free cholesterol in plasma and erythrocytes. Changes in other lipids are less pronounced.

Treatment of patients with leukodystrophies is carried out according to principles identical to the treatment of patients with intracellular lipoidosis.

Leukodystrophy is a large group of hereditary diseases with severe course which are associated with damage to the white matter of the brain. With this pathology, the metabolism of myelin is greatly impaired, but it is the myelin that covers each nerve fiber and is responsible for the correct transmission of impulses in the nervous system.

Forms of the disease

The disease is relatively rare and is diagnosed in several different forms.

Adrenoleukodystrophy is characterized by paralysis of the legs, which progresses rapidly, total loss their sensitivity, as well as poor adrenal functionality.

Metachromatic leukodystrophy is also manifested by impaired mobility, decreased muscle tone and tendon reflexes, there is a delay in physical development, there is a slowdown in mental development, loss of coordination, and unsteady gait.

Sudanophilic manifests itself in the form of nystagmus, optic nerve atrophy, decreased muscle tone, dementia, muscle tone and excessive small size brain

Globoid cell – constant tearfulness, convulsions, elevated temperature bodies, there are attacks of piercing scream.

Also among the forms, periventricular leukodystrophy should be highlighted.

Reasons

Unfortunately, it has not yet been possible to establish what exactly is the cause of the disease. It is clear that this is a genetic change in one or another enzyme. In some cases, such a mutation is hereditary and is transmitted to the child from parents who do not have any external manifestations.

But there are no fewer cases where this disease appears as a result of a completely random gene mutation. Because of improper metabolism destruction of the myelin sheaths of nerve trunks and pathways occurs. At the same time, foci of myelin death form in the brain, as well as places where the decay products of this tissue accumulate.

Symptoms

Leukodystrophy in a child does not begin to appear immediately after birth. In most cases, the newborn appears completely healthy. Development, both physical and mental, fully corresponds to age.

The first signs are a violation motor activity. The child begins to complain that it is difficult for him to walk and run, and problems with balance appear.

Then appears muscle weakness, which is expressed in greatly increased or, conversely, excessively decreased tone muscle tissue. Muscle twitching and convulsions may occur.

Leukodystrophy of the brain is also manifested by a gradual decline in memory and intelligence, and visual and hearing impairment is also noted. All previously acquired skills almost completely disappear.

At the most late stages– complete blindness, deafness, inability to swallow and move. Moreover, the sooner the first signs appear, the more severe and faster the disease will progress.

Diagnostics

Leukodystrophy of the brain in a child is diagnosed by the most in different ways. It could be:

1. CSF analysis.
2. Biochemical tests.
3. Computed tomography.
4. Genetic testing.

During diagnosis, the doctor must collect the available medical history, find out exactly when the first signs of the disease appeared, and how it all started. It is also necessary to know whether the disease is familial or has become a random gene mutation.

During the examination, attention is also paid to leukoaraiosis, in which the white matter of the brain is affected due to a lack of blood supply.

Metachromatic leukodystrophy, as well as two other forms, can be detected during pregnancy. After precise setting diagnosis, the woman is advised to terminate the pregnancy.

Treatment

To date, there is no treatment for leukodystrophy, including periventricular one. The main treatment is conservative symptomatic when certain signs of the disease appear.

The only method that will prolong the patient’s life is transplantation. bone marrow. However, it takes up to 2 years for new cells to begin to function, and this time in patients with this serious illness just no. In addition, such treatment does not in any way affect already developed mental or physical condition child.

Complications

The main complication is associated with damage to the myelin sheaths. This leads to the fact that the slow transmission of nerve impulses negatively affects motor and intellectual skills. Within a few years from the onset of the disease, complete mental degradation occurs, and then death.

Complications can also arise during bone marrow transplantation, in particular, it can be rejected.

Prevention

Genetic counseling at the stage of pregnancy planning, as well as during pregnancy, can prevent the birth of a child with this pathology. There is no specialized prevention of leukodystrophy.

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Pelyceus-Merzbacher is a disease that is the fourth form of leukodystrophy and can be transmitted in several ways.

The first is autosomal recessive. In this case, both parents must be carriers of the mutant gene. With a 50% chance their children will also be carriers of the damaged gene, and only with a 25% chance will they be born healthy child. The probability of having a child with this type of leukodystrophy is also the same.

The second is inheritance, which is linked to gender. For example, in a family, the disease is transmitted only to boys or only to girls.

What is the essence of the disease

Leukodystrophy of this type is considered one of the most severe. The basis of the disease is a violation of melanin metabolism, which results from the complete breakdown of the membranes of the brain. Melanin is a substance that ensures the transmission of signals throughout the central nervous system.

Disintegration of the membrane that covers all nerve endings, nerve cells, and the brain is a process that is constantly progressing and is irreversible. It is currently not possible to cure the pathology. The condition can be alleviated only with symptomatic treatment.

The disease primarily affects the white matter of the brain. Gray is affected to a lesser extent.

Causes and risk factors

According to statistics, pathology is diagnosed more often in boys than in girls. In 85% of all cases, marriages with close relatives occur.

What causes such a genetic failure, and why the disease in some cases appears spontaneously, that is, without any heredity, is not yet clear. As for risk factors, parents who are carriers of this pathology need to be especially careful.

Symptoms

The first symptoms begin to appear between 5 and 10 months of age. Moreover, at birth the child looks absolutely healthy, and even doctors cannot suspect anything is wrong. The development is slow, there may be a clear period during which there are no symptoms of the disease, and the duration of this period ranges from several months to a couple of years.

As mentioned above, in the first few months the child is no different from his peers. It all starts with a movement disorder, a coordination disorder. All this is accompanied by severe muscle weakness, muscle tone, which can be increased or greatly decreased, and convulsions are also observed.

As the disease progresses, the child loses all the motor skills that he had previously, that is, he stops sitting, rolling over, holding his head up, and walking. Since myelin is destroyed in the brain, problems begin with the intellect, and memory deteriorates. Moreover, it should be noted that the earlier the first symptoms appear, the worse the disease will progress.

Diagnostics

An MRI of the head will help to understand how severely the brain is affected in Pelizaeus-Merzbacher leukodystrophy. Sometimes genetic testing is required to determine whether parents are carriers of the defective gene.

Also, when talking with parents, the doctor will definitely collect the most detailed medical history in order to understand exactly when exactly the first signs of the disease appeared, how quickly the progression occurs, how much memory and intelligence suffers, and also how much physical activity has changed.

Treatment and prognosis

There is no cure for leukodystrophy. In some cases, a bone marrow transplant may help, but it will not be able to restore all the destroyed melanin and damaged nerve cells. And it takes a lot of time for the bone marrow to start working, and people with this diagnosis do not have it.

The second method of treatment is symptomatic. In this case, the child can only be saved from seizures, but other symptoms will continue to progress.

The prognosis for Pelizaeus-Merzbacher leukodystrophy is always unfavorable. The total life expectancy is no more than three years, and at the very end the child remains completely blind, deaf, unable to swallow and move.

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• Free lessons on treating low back pain from a certified physical therapy doctor. This doctor has developed a unique system for restoring all parts of the spine and has already helped more than 2000 clients with various back and neck problems!
• Want to know how to treat a pinched sciatic nerve? Then carefully watch the video at this link.
• 10 essential nutritional components for a healthy spine- in this report you will learn what your daily diet should be so that you and your spine are always healthy in body and spirit. Very useful information!
• Do you have osteochondrosis? Then we recommend studying effective methods of treating lumbar, cervical and thoracic osteochondrosis without drugs.

Leukodystrophy (progressive sclerosis of the brain) is a group of hereditary diseases of the nervous system. In patients with leukodystrophy, myelin deficiency leads to defenselessness and damage to the white matter of the brain, resulting in dementia. Symptoms appear gradually, and leukodystrophy itself can begin to develop in infancy or from 3 years, less often in adolescence.

Leukodystrophies are genetically determined diseases, and the probability of a child becoming ill is 25% if both parents are carriers of the disease.

Leukodystrophies belong to the group; however, there is both a diagnostic and therapeutic arsenal for this disease.

Symptoms of leukodystrophy:

• extreme irritability
• spasms in various parts of the body,
• weight loss,
• impaired control and coordination of movements,
• muscle paralysis or paresis,
• decreased vision,
• gradual deceleration general development, memory and intelligence,
• mental disorder.

Symptoms vary depending on the specific type of leukodystrophy and are sometimes difficult to recognize on early stages diseases: adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy or Krabbe disease. Diagnosis of leukodystrophy in Germany is aimed at determining the type of leukodystrophy and selecting appropriate therapy in each individual case.

Diagnosis of leukodystrophy in Germany

• Analysis family history diseases in three generations.
• Clinical examination.
• MRI of the brain (reveals white matter lesions characteristic of leukodystrophies).
• Computed tomography of the brain.
• Electromyography (with myelin deficiency, the impulse conduction time increases).
• Blood and urine analysis.
• Cerebrospinal fluid examination.
• Biochemical tests, measuring enzyme levels (to clarify the type of leukodystrophy).
• Molecular genetic examination.
• Prenatal (prenatal) diagnostics. Possible for metachromatic, globoid cell and adrenoleukodystrophy.

Treatment of leukodystrophy in Germany

The main treatment method for leukodystrophies in Germany is currently bone marrow transplantation (or cord blood) in the early stages of the disease. In a favorable case, the operation can lead to normalization of the level of the missing protein, and in the future – to an improvement in the quality of life and an increase in its duration. Bone marrow transplantation stops the progression of the disease and allows one to preserve motor and intellectual functions.

If bone marrow transplantation is not possible or recommended, then therapy aimed at alleviating the symptoms of the disease remains. Treatment for most patients with leukodystrophy is supportive and includes German medications, a special diet, physical health activities, communication programs, neurological rehabilitation.

The effectiveness of treatment of leukodystrophy in German clinics is due to the fact that here throughout last tens years special attention devoted to the study and Doctors are dedicated to providing effective assistance to everyone who contacted them. You will receive high-quality diagnostics, professional advice and support from specialists.

Leukodystrophies – a group of severe hereditary metabolic diseases characterized by damage to the white matter of the brain. Metabolism is impaired in leukodystrophies myelin, that is, a substance that forms the sheath of nerve processes and ensures effective transmission of signals in the nervous system (myelin is what 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 to function. A defect in one of these genes can impair the formation or maintenance of myelin sheaths. in good condition. The transmission of nerve signals slows down sharply, motor and intellectual disorders, the perception of signals from the senses deteriorates. With further destruction of myelin, these disorders intensify, over several years leading to deep physical and mental degradation and then to the death of the patient. is so far the only method to stop or slow down the progression of the disease in some patients.

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

• Adrenoleukodystrophy. Substances of a special type accumulate in tissues - fatty acids with very long chains, since their splitting in this disease is impaired. As a result, the structure and function of myelin are disrupted.
• Metachromatic leukodystrophy caused by a deficiency of the enzyme arylsulfatase A. Sulfatides accumulate in the body - substances that have a destructive effect on myelin.
• Globoid cell leukodystrophy, or Krabbe disease, is associated with a disruption in 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.

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

Incidence and risk factors

Leukodystrophies – rare diseases. Thus, 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 becoming ill is 25% if both parents are carriers of the disease. Such diseases affect boys and girls with equal frequency. They occur more often in communities where consanguineous marriages are common, and may occur with varying frequencies among different nations.

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

For families who have already had children with any type of leukodystrophy, consultation with a geneticist is recommended before the birth of all subsequent children.

Signs and symptoms

At birth, children with leukodystrophy usually appear healthy and take some time to develop according to their 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.

The usual ones are movement disorders. In children, coordination of movements worsens, problems with balance are noted, and it becomes difficult to walk and run. Possible muscle weakness, abnormally increased or decreased muscle tone, muscle twitching. Appear seizures. Changes in behavior occur. Memory and intelligence gradually decline. Vision and hearing deteriorate. The child gradually “rolls back” in his development, losing previously acquired motor and intellectual skills. On late stages As the disease progresses, blindness, deafness, paralysis, and the inability to swallow food normally occur. As a rule, the earlier in age signs of the disease appear, the faster it progresses.

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

Diagnostics

Damage to the white matter of the brain, characteristic of leukodystrophies, is detected by magnetic resonance imaging (MRI). Typically, MRI abnormalities associated with myelin destruction 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. In many leukodystrophies, the cerebrospinal fluid reveals 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.

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

Treatment

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

At the same time, the use of transplantations for leukodystrophies is associated with serious limitations. It is very important to carry out transplantation as early as possible, before the development of noticeable neurological disorders. Indeed, transplantation does not allow to “correct” 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.

Thus, 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 some more time passes (for example, in some leukodystrophies we can talk about 12 or even 24 months) until the work of donor cells leads to normal functioning myelin. And all this time the development of the disease will continue. Therefore, in forms with very early onset diseases of hope are associated mainly with those transplantations that were performed before the onset of clinical symptoms (for example, if the eldest child in the family had already been diagnosed with leukodystrophy and therefore youngest child produced early diagnosis). With a slower progression of the disease, the chances of success increase.

If bone marrow transplantation is not possible or recommended, then palliative therapy remains, aimed at alleviating the symptoms of the disease. New treatment approaches are constantly being developed, but for now they remain experimental.

There is an opinion that it is possible to slightly slow down the development of adrenoleukodystrophy (including while awaiting transplantation) with the help of special diet. Sometimes Lorenzo's 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 usually poor, especially in forms of the disease with early onset and rapid progression of symptoms. However, some patients may benefit from allogeneic bone marrow or cord blood transplantation. If successful, it stops or slows down the progression of the disease and allows one to largely preserve motor and intellectual functions. At the same time the most important condition is timely transplantation.