Friedreich's ataxia – hereditary disease nervous system, autosomal recessive type of inheritance. The disease is characterized by a syndrome of damage to the posterior and lateral cords spinal cord, more often in the lumbosacral segments, by the death of cells of Clark's columns and dorsal spinocerebellar tracts.
On late stages characterized by nuclear degeneration cranial nerves, dentate nucleus, cerebellar peduncle, cells of the cerebral hemispheres are somewhat less likely to suffer.
Reasons for the development of Friedreich's ataxia
The development of the disease is associated with an imbalance of intracellular iron; its high concentration in mitochondria causes an increase in free radicals that destroy the cell. An imbalance occurs when there is insufficiency or distortion of the structure of the protein synthesized in the cytoplasm - frataxin . This protein is responsible for the transport of iron from mitochondria, and when it accumulates above normal levels, a decrease in cytosic iron occurs.
These are the main reasons for the development of Friedreich's ataxia, as a result of which genes encoding are activated ferroxidase
And permease
, which, like frataxin, are responsible for iron transport.
This leads to even greater accumulation in the mitochondria. Heredity is caused by the so-called Friedreich's disease gene, presumably found in the centomeric region of the 9th chromosome at the 9ql3 - q21 locus. Several may occur
one gene, which causes different shapes diseases. Friedreich's ataxia accounts for half of the cases of ataxia. The first signs appear before the age of 20, much less often before the age of 30. It occurs equally often in both women and men; only representatives of the Negroid race
The disease affects the neurons of the central and peripheral nervous system, but medicine has no explanation as to why only the spinal cord pathways in the nervous system are damaged. In other systems, at least as many important cells organs, these are myocardial cells, β - cells of the islets of Langerhans in the pancreas, cells of the retina and bone tissue.
The course of the disease is constantly progressive. If missing adequate treatment Friedreich's ataxia, the duration of the disease does not exceed 20 years. And starting to show awkwardness and uncertainty when walking, after a while it completely deprives a person of normal coordination of movements and moving independently. The disease is fatal; in rare cases, in the absence of such manifestations as heart disease, patients live up to 70-80 years.
Symptoms of Friedreich's ataxia
The first symptoms of the disease are suppression of the Achilles and knee reflexes. These symptoms appear several years before the appearance of others, and early manifestations also include rheumatic carditis , which is often treated as a separate disease. So these are not considered to be symptoms of Friedreich's ataxia until neurological damage occurs. Gradual skeletal deformities occur, such as scoliosis, finger and toe deformities, and Friedreich's foot, in which there is abnormal extension of the fingers in the main phalanges and the foot has a high concave arch.
Friedreich's ataxia in its expanded form is characterized by neurological disorders typical of ataxias and total areflexia . Muscular and vibration sensitivity, muscle hypotonia, and Babinski's symptom are impaired. Sensitive and atrophy and weakness of the leg muscles gradually develops.
In 90% of patients, extraneural manifestations occur, these are heart lesions, endocrine disorders , . A progressive cardiomyopathy , it can be either hypertrophic or dilated. In this case, symptoms of Friedreich's ataxia are observed, such as pain in the heart area, palpitations, systolic murmurs, etc. Characteristic endocrine diseases, such as diabetes , hypogonadism , .
The late stage of ataxia is characterized by amytrophy and a disorder of deep sensitivity, the disappearance of tendon and periosteal reflexes. What does it cover? upper limbs. Deep disintegration occurs motor functions, due to which a person loses the ability to walk and take care of himself. Developing kyphoscoliosis with the formation of a hump, deformation of the hands. Extraneural manifestations may include nystagmus, hearing loss, atrophy optic nerves, dysfunction of the pelvic organs, . The disease, which progresses in the later stages, is the cause of death in half of the patients, most often due to disturbances in the cardiac wiring system. Immediate causes of death also include pulmonary failure and infectious complications.
Diagnosis of Friedreich's ataxia
Computed tomography of the brain, which remains the main diagnosis of ataxia in this disease, is ineffective; a number of changes can be detected only in late stages. This is due to the spinal localization of changes, so it is possible to detect only weak degree atrophy of the cerebellum at an early stage and atrophy of the hemispheres, expansion of the stem cisterns, lateral ventricles and subarachnoid space of both hemispheres at later stages. Early diagnosis Friedreich's ataxia is produced using MRI , which makes it possible to detect atrophy of the spinal cord, and at an advanced stage, moderate atrophy of the pons, cerebellum and medulla oblongata. On initial stage An electrophysiological study is required; during such studies, the severity of damage to the sensitivity of the nerves of the limbs is established.
For full diagnostics carry out load tests glucose tolerance, x-ray examination of the spine. First of all, diagnostics is aimed at accurately establishing a diagnosis and differentiating the disease from others with similar symptoms. For example, the symptoms of Friedreich's ataxia may be the same as those of hereditary ataxia with deficiency, Bassen-Kornzweig syndrome, hereditary metabolic diseases such as Krabbe disease And Niemann-Pick disease. Similar symptoms may also occur with, with the exception of tendon areflexia, muscle hypotonia and extraneural manifestations. It is not typical for Friedreich's ataxia to have remissions and changes in the density of brain matter, which is observed in the diagnosis of multiple sclerosis.
To differentiate the disease, a number of additional laboratory research. DNA testing and medical genetic counseling, blood lipid profile examination, blood smear analysis for the presence of vitamin E deficiency and acanthocytes. Treatment of Friedreich's ataxia does not lead to full recovery, but timely prevention makes it possible to avoid the development of many symptoms and complications. Diagnosis of Friedreich's ataxia using DNA testing should be prescribed not only to the patient, but also to relatives to determine the heredity of the disease; this is necessary for the purposes of prevention and prescribing preventive therapy.
Treatment of Friedreich's ataxia
To slow the progression of the disease, they are prescribed mitochondrial drugs
, antioxidants
and other drugs that reduce the accumulation of iron in mitochondria.
Antioxidants such as vitamins A And E , as well as a synthetic substitute coenzyme Q 10 – , which inhibits the neurodegenerative process and development hypertrophic cardiomyopathy. Also appointed 5-hydroxypropane , which gives good results, but it requires further research.
In general, treatment is symptomatic and should eliminate symptoms of Friedreich's ataxia such as diabetes , . Also carried out surgical correction stop and introduction botulinum toxin into spastic muscles.
AND physiotherapy - procedures without which treatment of Friedreich's ataxia most often turns out to be ineffective. Constant exercise makes it possible to keep the body in good shape and eliminate painful sensations. Patients require social adaptation, since many have to live in a state of complete helplessness. Loss of vision, the ability to move independently, impaired coordination creates psychological disorders, which should be eliminated with the help of specialists and the support of loved ones.
Hereditary Friedreich's ataxia (FA) is a disease in which damage to the nervous system according to a degenerative scenario.
It is autosomal recessive (the disease manifests itself if the child has inherited the gene for the disease from both parents), characterized by a mutation in the gene responsible for encoding a protein called frataxin (a mitochondrial protein responsible for the removal of iron). The disease was named after German doctor Nikolaus Friedreich (1825-1882), who described her at the age of 35.
Ataxias are diseases that cause incoordination of muscle movement.
According to statistics, AF is considered the most common of ataxias, accounting for 2 to 7 cases per 100 thousand population, with an amount of 1 carrier per 120 people.
Causes of the disease
When the gene is mutated, iron accumulates in the mitochondria. which leads to an excess of iron, and the accumulation of free radicals and various damages(due to their uncontrolled chemical activity).
First of all, neurons, heart muscle cells, pancreatic cells responsible for insulin synthesis, retinal cells and bone cells are affected. All these lesions lead to the appearance characteristic symptoms AF in central and peripheral parts nervous system, diabetes, myocardiopathy, visual disorders and bone deformities.
Loss of sensitivity or - prevention, causes and treatment of the disease. Complex of disorders or hypothalamic syndrome puberty- what is typical for the syndrome at a given age and what modern medicine offers.
Clinical picture
In most cases, the first manifestations of Friedreich's ataxia are characteristic of the age from 10 to 20 years, but with less frequency the onset of the disease is possible in the third and fourth decades of life.
At first the patient's gait is disturbed— she becomes shaky and insecure. Frequent trips and falls are common.
The second ones observed hand movement disorders, trembling appears, which leads to changes in handwriting. Further speech is impaired- it becomes slow and unintelligible, decreases auditory function and is present constant weakness in the legs.
Neurology distinguishes two types of AF cerebellar and sensory.
It is difficult for the patient to perform the Romberg pose (standing position, legs together, eyes closed, arms extended forward), misses when attempting the heel-knee test (lying on your back with eyes closed, we raise one leg high and try to hit the knee of the other leg with the heel) and the toe-to-toe test (get your finger on closed eyes at the tip of the nose).
The Achilles and knee reflex disappear. Developing Babinski syndrome- when the outer side of the foot is irritated, extension occurs thumb legs.
If the disease progresses, then there is a total loss of periosteal and tendon reflexes, and a violation of vibration sensitivity and joint-muscular sensation occurs.
In the photo, a symptom of Friedreich's hereditary ataxia - Friedreich's foot
Happening loss of muscle tone and paresis various muscles primarily in the distal sections lower limbs. Then the arm muscles are affected, causing the person to lose the ability to self-care.
Some develop (acquired dementia) and pelvic disorders, which may be accompanied by shifting eyes, blindness due to optic atrophy and hearing loss.
Outside the nervous system the following are observed: violations:
- In 90% of cases heart muscle damage causing arrhythmia and heart failure.
- Friedreich's foot- a foot with a high and concave arch, with bent extreme phalanges and straightened main ones. Club feet, scoliosis, and curvature of the arms and legs are also noted.
- Endocrine disorders- infantilism (preservation of signs of earlier stages of growing up), diabetes mellitus, hypogandism ( appearance With feminine features due to decreased androgen production) in men, ovarian dysfunction in women. Rarely, cataracts occur.
Diagnostic techniques
Often, patients with extraneural manifestations of AF are seen by a neurologist only after the onset of neurological symptoms.
Before this, they can be treated for several years without much success by a cardiologist for arrhythmia, or by an orthopedist for bone curvatures.
For instrumental diagnosis of hereditary Friedreich's ataxia, use magnetic resonance imaging, which allows us to identify atrophic changes V medulla oblongata and cerebellum, in the spinal cord there is a decrease in its diameter and other atrophic degradation.
Computed tomography it makes sense to use only in the later stages of the disease, since early stages it can only detect cerebellar atrophy.
The brain pathways are studied using transcranial magnetic stimulation based on the laws of magnetic induction; peripheral nerves are studied using electroneurography and electromyography.
In AF, there is a significant decrease in action potentials along motor nerve fibers against the background of loss up to complete absence sensitivity.
If there are extraneural manifestations of AF, then apply appropriate to these symptoms additional methods research. It is of no small importance to study the patient’s genetics through DNA diagnostics.
The patient's blood samples are compared with his parents and other blood relatives. At the stage of pregnancy, AF can be detected at 8-12 weeks of DNA diagnosis of chorionic villi or at 16-24 weeks by examining amniotic fluid.
Healing procedures
Due to the genetic nature of the disease, all treatment methods are limited to delaying the progression of the disease, which allows long time avoid complications and maintain an active lifestyle.
Three types of metabolic drugs are used to treat FA: drugs:
- cofactors of enzyme reactions (increase the number of reactions);
- stimulants respiratory function mitochondria;
- antioxidants (substances that slow down oxidation).
Additionally, cardiac drugs that improve metabolism in the heart muscle, neuroprotectors, and nootropics (drugs that activate cognitive functions) are used. 
In cases muscle spasms botulinum toxin is used in the form of intramuscular injections, in the presence of bone curvature, surgical operations are performed.
Physiotherapy aimed at training coordination and muscle strength can effectively resist the degrading effect of AF and reduce pain.
In diet patients should reduce their intake of carbohydrates, an excess of which leads to worsening symptoms.
Forecast
Friedreich's ataxia is characterized by a steadily progressive course, which sooner or later leads to death. Death occurs due to cardiac or respiratory failure.
According to statistics Approximately 50% of patients do not survive to 35 years of age.
In women, the disease lasts at least 20 years, and for men this figure is 2/3. Occasionally if not diabetes mellitus and heart problems, the patient can live to an old age and overcome the 70-year mark.
Video: Friedreich's ataxia
Hereditary degenerative disease Friedreich's ataxia. Doctor giving a lecture medical sciences Kotov N.S.
When in Everyday life we perform precise movements, we don’t think about what complex mechanisms they are provided in the central nervous system. Man lives full life, dances, plays sports, can play football, skate - and the movements bring pleasure. Figure skating is the limit of the ability of the coordination-motor systems of the central and peripheral nervous system of a person. To achieve success, a person achieves through hard training high degree development of nerve contacts in the cells of the cortex, diencephalon, brainstem and cerebellum. At the same time, success in developing these connections can only be achieved in at a young age when the nervous system has a high “neuroplasticity potential.” Neuroplasticity is the ability of the nervous system to change due to perceived external influences or one’s own “internal” activity, for example, during a series of repeated specific movements when playing the musical instrument or playing sports. The property of neuroplasticity underlies the human ability to remember and reproduce. In order to develop a skill, as a rule, a series of repetitions of unidirectional influence is needed - it triggers processes in the central nervous system that lead to electrophysiological and biochemical changes. As a result, new contacts (synapses) are formed between the cells of the central nervous system or old contacts are activated. Thus, the skill of harmonious, subtle movement cannot be formed due to the fact that in ataxia the substrate of its formation - the nervous tissue - is damaged. Many complexly interconnected structures are responsible for the coordination of movements in the human brain, which, in particular, include the cerebral cortex, the cerebellum, the diencephalon, various structures of the brain stem, the segmental apparatus of the spinal cord, connecting it with conductive structures located in the brain pathways and, finally, peripheral nerves and their receptor apparatus, located in the muscles, periosteum, and deep layers of the skin. In humans, the cerebellum is located inside the skull in the back cranial fossa, i.e. approximately at the level of the place where everyone can easily identify the back of their head. The cerebellum consists of two hemispheres, three pairs of legs, through which it is connected to other structures of the brain and the so-called vermis.
The hemispheres are largely responsible for precise and harmonious movements in the limbs, and the worm is responsible for maintaining posture and balance. When a person tenses certain muscle groups while performing a targeted movement or maintaining a posture, the cerebellum receives nerve impulses from the part of the cerebral cortex that is responsible for movement (precentral gyrus) and along sensory fibers from muscles and tendons through the spinal cord. Passing complex system contacts, both in the region of the spinal cord segments and at the level of the trunk, the flow of nerve impulses reaches the cerebellum. The cerebellum “analyzes” it and produces its “response”, which is sent both to the cortex (reaches the human consciousness) and to the segmental level of the spinal cord. The entire system as a whole “adjusts” the work of the muscles so that it becomes clear, harmonious, beautiful - like that of figure skaters...
The term "ataxia" literally means "disorder", "confusion", "confusion", "confusion"; in this meaning it has been used since the time of Hippocrates for a very long time.
Ataxia itself is a violation of the simultaneous coordinated work of all muscle groups to optimally achieve the goal of a motor act.
The most common ataxia is Friedreich's ataxia, which occurs in all nations. There is no Friedreich's disease only among representatives of the Negroid race. The disease begins before age 25.
General information about Friedreich's ataxia
Thus, the most active cells in the body suffer human body- these are neurons of the central and peripheral nervous system, cells of the heart muscle (myocardium), β - cells of the islets of Langerhans of the pancreas, cells of the retina and skeletal system. Why only the spinal cord pathways in the nervous system are affected is unknown to science. Are developing following symptoms: ataxia, dysarthria, muscular hypotonia, muscular dystonia, deep sensitivity disorders, Babinski's symptom, tendon areflexia, amyotrophy, paresis, electrophysiological signs of sensory polyneuropathy, hypertrophic cardiomyopathy, ECG changes, diabetes mellitus, hypogonadism, short stature, optic atrophy, cataract, retinitis pigmentosa. Bone deformities - kyphoscoliosis (curvature of the spine with the formation of a hump), Friedreich's foot (characterized by a high arch), hand deformities.
Causes of Friedreich's ataxia
The development of the disease is associated with a deficiency or distorted structure of the frataxin protein, which is synthesized inside the cell in the cytoplasm; its function is to transport iron from the mitochondria. Mitochondria are the “energy stations of the cell”; the accumulation of iron in them (iron oxidation is a universal mechanism for oxygen transport in the body) is associated with high activity oxidative processes inside them. With an increase in iron content in mitochondria by more than 10 times, total cellular iron remains within the range normal values, and the content of cytosolic iron decreases. This leads to the activation of genes encoding iron transporting enzymes - ferroxidase and permease. Thus, the imbalance of intracellular iron is further aggravated. High concentration iron in mitochondria leads to an increase in the number of free radicals, which have a damaging effect on the cell. Friedreich's hereditary ataxia is the most common of all ataxias.
Symptoms of Friedreich's ataxia
The diagnosis is made based on the following clinical signs:
- autosomal recessive inheritance (i.e., not related to sex, and the disease gene appears only if there are two identical copies of the gene, although other options are possible);
- onset of the disease before 25 years of age;
- progressive ataxia;
- dysarthria;
- tendon areflexia (lack of involuntary contraction muscles in response to a blow to the tendon with a neurological hammer);
- Babinsky's symptom (a sign of damage to the so-called pyramidal system, which is responsible for voluntary movements. Characterized by dorsiflexion and abduction of the big toe and fan-shaped spreading of the remaining toes. Characteristic for children under 6 months);
- loss of deep sensitivity in the distal parts of the extremities (for an explanation of the term “deep sensitivity”, see the article Guillain-Barré syndrome);
- electrophysiological signs of axonal and sensory neuropathy.
- changes on the ECG.
All patients need to undergo medical genetic counseling and DNA testing. This is important to do to distinguish this disease from a number of others accompanied by similar manifestations, for example, with genetically determined or acquired deficiency of vitamin E and others fat-soluble vitamins, which is accompanied by a decrease in the antioxidant potential of neurons. For adequate diagnosis of isolated or combined vitamin E deficiency conditions, it is necessary to determine the content of vitamin E in the blood, examine lipid profile blood and a blood smear for the presence of acanthocytes (erythrocytes with an altered stellate membrane) It is necessary to distinguish Friedreich's ataxia from other hereditary metabolic diseases such as gangliosidosis, Krabbe disease, Niemann-Pick disease (the content of sphingomyelins in the cerebrospinal fluid is determined).
Prevention of Friedreich's ataxia
Of particular importance is DNA testing at an early presymptomatic stage in order to prescribe preventive therapy. The patient's relatives are examined first.
Diagnosis of Friedreich's ataxia
The diagnosis can be suspected clinically.
The following symptoms develop: ataxia, dysarthria, muscle hypotonia, muscular dystonia, deep sensitivity disorders, Babinski's symptom, tendon areflexia, amyotrophy, paresis, electrophysiological signs of sensory polyneuropathy, hypertrophic cardiomyopathy, ECG changes, diabetes mellitus, hypogonadism, short stature, optic atrophy , cataracts, retinitis pigmentosa. Bone deformities - kyphoscoliosis (curvature of the spine with the formation of a hump), Friedreich's foot (characterized by a high arch), hand deformities.
Neurophysicalization methods are also used - MRI, DNA diagnostics.
Treatment of Friedreich's ataxia
There is no treatment leading to complete recovery. Drugs of the so-called mitochondrial series, antioxidants and compounds that help reduce the accumulation of iron in mitochondria are used. Among the antioxidants, vitamins A and E are widely used, as well as the drug idebenone (Noben), which is a synthetic analogue of coenzyme Q 10. The drug has a powerful antioxidant and cytoprotective effect, which helps to “slow down” the neurodegenerative process. In addition, the target organ of idebenone is the myocardium, thus the drug slows down the development of hypertrophic cardiomyopathy. If Friedreich's ataxia is detected in children, observation by an endocrinologist and orthopedic correction of the feet (Friedreich's foot) are necessary. Great importance also has physical therapy and physiotherapy.
Familial Friedreich's ataxia- chronic progressive disease, the main clinical manifestation which is ataxia, caused mainly by combined damage to the spinal systems.
The disease is hereditary and is transmitted in an autosomal recessive manner. Among the parents of patients, an increased frequency of consanguineous marriages was noted.
A characteristic pathological sign of Friedreich's ataxia is degeneration of the posterior and lateral columns of the spinal cord. Gaulle's bundles are affected to a greater extent than Burdach's bundles. The cells of Clark's columns and the posterior spinocerebellar tract starting from them suffer. Damage to the pyramidal tract usually begins with lumbar region. Degeneration of the spinal tracts can be traced to the medulla oblongata. It is assumed that certain disturbances in the metabolism of amino acids and a decrease in the activity of cerebral cholinergic systems may be important in the biochemical mechanisms of the pathogenesis of the disease.
Clinical picture .
The main symptom of the disease is the gait of patients was designated by Charcot as tabetic-cerebellar. Patients walk with their legs spread wide apart, deviating from the straight direction in both directions; gait is uncertain, clumsy. Static ataxia is also observed; often noted positive symptom Romberg. As the disease progresses Coordination problems extend to the arms and muscles chest, face.
Handwriting is disrupted, peculiar ataxic breathing disorders may develop, and facial expressions change. Speech is slow, unmodulated, jerky. There may be dysmetria, dysdiadochokinesis, various hyperkinesis, usually accompanying active movements. Muscle tone is reduced. In the later stages of the disease, lower spastic paraparesis may develop.
Characteristic and early sign illness is absence or decrease in tendon and periosteal reflexes. First of all, tendon reflexes fade in the legs, then areflexia spreads to the upper limbs. With the development of spastic paraparesis, tendon reflexes may reappear. Often, especially in the later stages of the disease, it is possible to evoke the pathological Babinski reflex, protective reflexes.
Characteristic decreased deep sensitivity. Superficial types of sensitivity are usually not affected. TO characteristic features The disease includes large-scale nystagmus.
Otoneurological examination in most cases reveals bilateral vestibular areflexia or asymmetry of reflex nystagmus. A number of patients have decreased hearing.
Optic nerve atrophy and oculomotor nerve damage Unlike cerebellar ataxia are rare. Along with this, changes in visual evoked potentials are detected with great consistency.
In most cases, intelligence is preserved. However, mental retardation of varying degrees may occur.
On EEG - disturbance of alpha and beta rhythm, presence of irregular sharp waves and groups of slow oscillations.
Friedreich's ataxia is characterized by various extraneural abnormalities; the most common of them are skeletal changes and heart damage. The first are expressed in kyphoscoliosis and a characteristic change in the shape of the foot (increase in the arch and extension of the fingers, mainly the first finger in the main phalanx; a tendency to frequent dislocations of the joints).
Heart damage manifested by tachycardia, paroxysmal pain in the region of the heart, shortness of breath during physical exertion, expansion of the boundaries of the heart, systolic murmur. The ECG shows rhythm disturbances, changes in atrioventricular and intraventricular conduction, and deformation of the atrial wave. Patients often experience birth defects hearts.
In some cases, Friedreich's ataxia is combined with which in this form of hereditary ataxia is more common than in the general population. From others endocrine disorders Infantilism and hypogonadism may occur. In isolated cases, Friedreich's ataxia is combined with congenital cataracts. Clinically healthy relatives of patients with Friedreich's ataxia often exhibit individual signs, characteristic diseases, primarily nystagmus and decreased or absent tendon reflexes.
Certain anomalies are characteristic of certain families. In all likelihood, they should be considered as phenotypic manifestations of heterozygous carriage of a pathological gene. However, in childhood, these signs may be the first symptoms of a developing disease.
In most cases, the disease begins at the age of 6-13 years, and is then characterized by slow but steady progression. Various infections and other harmful exogenous factors can contribute to the development of the disease and worsen its course. In some families, Friedreich's ataxia occurs atypically: along with ataxia, symptoms characteristic of cerebellar ataxia, familial spastic paraplegia, and neural amyotrophy may appear. In rare cases, the disease is inherited in an autosomal dominant manner.
At computed tomography and morphological examination may reveal cerebellar atrophy. These cases are considered as intermediate forms between these diseases; it is assumed that they are caused by independent genes.
Ataxia can be combined with pathological pyramidal symptoms at multiple sclerosis. The latter disease differs from Friedreich's disease in its later onset, remitting course, in most cases the diffuse nature of the process, as a rule, increased deep reflexes, changes in the fundus of the eye, frequent oculomotor disorders, and lack of familiality.
Treatment is symptomatic.
- Apply special system therapeutic exercises, aimed primarily at reducing coordination disorders. When prescribing exercises, it is necessary to take into account the possibility of cardiac pathology, in the presence of which appropriate therapy is prescribed.
- Shown general strengthening agents (vitamins),
- Drugs affecting tissue metabolism (piracetam, aminalon, acephen, cerebrolysin), treatment which should be repeated periodically.
What is Friedreich's disease
Friedreich's familial ataxia is a hereditary degenerative disease of the nervous system, characterized by a syndrome of damage to the posterior and lateral cords of the spinal cord. The type of inheritance is autosomal recessive, with incomplete penetrance of the pathological gene. Men and women get sick equally often.
Causes (etiology) of Friedreich's disease
Friedreich's disease is the most common form hereditary ataxias, the prevalence is 2 - 7 per 100,000 population. The type of inheritance is autosomal recessive. The Friedreich's disease gene was mapped to the centomeric region of chromosome 9 at the 9ql3 - q21 locus. It is assumed that classical and atypical shape Friedreich's diseases can be caused by different (two or more) mutations of the same gene. Mapping of the Friedreich's disease gene led to the development of methods for indirect DNA diagnosis of the disease (including early and prenatal diagnosis) and diagnosis of heterozygous carriage of the mutant gene.
Pathogenesis (what happens?) during Friedreich's disease
Are detected degenerative changes in the conductive tracts of the posterior and lateral cords of the spinal cord, mainly the Gaulle fascicles, to a lesser extent – Burdach, Flexig, Gowers, fibers of the pyramidal tract, dorsal roots, as well as in the cells of the cerebellar cortex, subcortical ganglia, and cerebral cortex.
Symptoms ( clinical picture) Friedreich's disease
The first symptoms of the disease most often occur in the prepubertal period. They are characterized by a combination of typical neurological and extraneural manifestations. The disease usually manifests itself with the appearance of awkwardness and uncertainty when walking, especially in the dark; patients begin to stagger and often stumble. Soon, ataxia when walking is accompanied by incoordination in the hands, changes in handwriting, and weakness in yoga. Already at the very beginning of the disease, dysarthria may be noted. An early and important differential diagnostic sign of Friedreich's disease is the disappearance of tendon and periosteal reflexes. Suppression of reflexes (primarily Achilles and knee) can precede the manifestation of other symptoms of the disease by several years and be the most early manifestation neurological dysfunction. In the advanced stage of the disease, patients usually experience total areflexia. A typical neurological manifestation of Friedreich's disease is a violation of deep (articular-muscular and vibration) sensitivity. Quite early in patients, a neurological examination may reveal Babinski's symptom, muscle hypotonia. As the disease progresses, cerebellar and sensory ataxia, weakness and atrophy of the leg muscles gradually increase. In the late stage of the disease, amyotrophy and deep sensitivity disorders that spread to the hands are common. Patients stop walking and caring for themselves due to the profound breakdown of motor functions. In some cases, nystagmus, hearing loss, and optic nerve atrophy are observed; with a long course of the disease, dysfunction is observed pelvic organs, dementia.
Among the extraneural manifestations of Friedreich's disease, it is necessary to highlight cardiac damage, which, according to our data, occurs in more than 90% of patients. The development of a typical progressive cardiomyopathy is characteristic. Cardiomyopathy is predominantly hypertrophic in nature, but in some cases, as follows from our observations, the development of dilated cardiomyopathy is possible. It is possible that these heart changes in Friedreich's disease are various stages one process. Cardiomyopathy is manifested by pain in the heart area, palpitations, shortness of breath during physical activity, systolic murmur and other symptoms. In more than half of patients, cardiomyopathy is the direct cause of death. Corresponding changes are usually detected on the ECG (arrhythmia, T wave inversion, conduction changes) and echocardiography. In some cases, clinical and electrocardiographic symptoms of cardiac damage sometimes precede the appearance of neurological disorders by several years. Patients are observed for a long time by a cardiologist or local physician, most often with a diagnosis of rheumatic heart disease.
Another characteristic extraneural manifestation of Friedreich's disease is skeletal deformities: scoliosis, “Friedreich's foot” (high concave arch of the foot with hyperextension of the fingers in the main phalanges and flexion in the distal phalanges), deformation of the fingers and toes, etc. These disorders can also appear long before the development of the first neurological symptoms.
Extraneural manifestations of Friedreich's disease include endocrine disorders (diabetes mellitus, hypogonadism, infantilism, ovarian dysfunction), cataracts. It is generally accepted that extraneural signs of Friedreich's disease are a manifestation of the pleiotropic effect of one mutant gene.
Friedreich's disease is characterized by a steadily progressive course, the duration of the disease usually does not exceed 20 years. The immediate causes of death may be heart and pulmonary failure, infectious complications.
Diagnosis of Friedreich's disease
Diagnosis of the disease is most difficult in cases where Friedreich's ataxia begins with extraneural manifestations. At the same time, some patients are observed for several years by a cardiologist for heart disease or by an orthopedist for scoliosis. Only when neurological symptoms develop do they go to a neurologist for consultation.
Main methods instrumental diagnostics Friedreich's ataxia is magnetic resonance imaging and neurophysiological testing. MRI of the brain reveals atrophic processes in the medulla oblongata and pons, and cerebellar atrophy. MRI of the spine shows a decrease in the diameter of the spinal cord and its atrophic changes. In making the diagnosis of Friedreich's ataxia, CT scan of the brain is not informative enough. With her help characteristic changes can only be visualized in late stages of the disease. Early ataxia Friedreich's disease is accompanied only by CT signs of slight cerebellar atrophy.
The study of pathways is carried out using transcranial magnetic stimulation, the study peripheral nerves- by electroneurography and electromyography. At the same time, Friedreich's ataxia is characterized by a moderate decrease in action potentials when carried out motor nerves in combination with a large (up to complete disappearance) decrease in conductivity along sensitive fibers.
Due to the presence of extraneural manifestations, Fredreich's ataxia requires additional research cardiovascular, endocrine and musculoskeletal systems. For this purpose, a consultation with a cardiologist, orthopedist, ophthalmologist and endocrinologist is carried out; blood sugar analysis and glucose tolerance test, research hormonal levels; ECG, stress tests, ultrasound of the heart; X-ray of the spine.
Of no small importance in establishing the diagnosis of Friedreich's ataxia is medical genetic counseling and comprehensive (direct and indirect) DNA diagnostics. It is performed on blood samples from the patient, his biological parents, and blood brothers and sisters. During pregnancy, Friedreich's ataxia in the fetus can be diagnosed using DNA diagnostics of chorionic villi at 8-12 weeks of pregnancy or amniotic fluid at 16-24 weeks.
Friedreich's ataxia requires differential diagnosis with funicular myelosis, cerebellar tumor, neurosyphilis, metabolic hereditary diseases(Niemann-Pick disease, Krabbe disease, Louis-Bar syndrome, hereditary vitamin E deficiency), multiple sclerosis.
Treatment of Friedreich's disease
Apply symptomatic remedies: restorative drugs, physical therapy, massage. In some cases, surgical correction of foot deformities is performed.
Forecast
Friedreich's ataxia has a steadily progressive course, leading to death. The patient dies from cardiac or respiratory failure, infectious complications. About 50% of patients who develop Friedreich's ataxia do not live past 35 years of age. In women, the course of the disease is more favorable. Their life expectancy is 100% more than 20 years from the onset of ataxia, while among men only 63% live longer than this period. In extremely rare cases, in the absence of heart disorders and diabetes, patients live up to 70-80 years.
Which doctors should you contact if you have Friedreich's disease?
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