Friedreich's disease (Friedreich's ataxia). What is Friedreich's ataxia, diagnosis and treatment Jewish hereditary disease Friedreich's ataxia

A genetic disease associated with impaired transport of iron from mitochondria and proceeding with a predominant lesion of cells of the central and peripheral nervous system, cardiomyocytes, β-cells of the pancreas, cells of bone tissue and retina. Friedreich's ataxia is diagnosed using MRI of the brain and spinal cord, neurophysiological studies, and genetic diagnostics. Additionally, an ECG, an ultrasound of the heart, a study of the hormonal background, and an x-ray of the spine are performed. Friedreich's ataxia is treated with metabolic and symptomatic drugs, diet, regular exercise therapy. Surgical treatment is used to eliminate bone deformities.

ICD-10

G11.1 Early cerebellar ataxia

General information

Friedreich's ataxia was described in 1860 by a German physician, whose name the disease still bears. Friedreich's ataxia belongs to the group of ataxias, which also includes cerebellar ataxia, Pierre-Marie's ataxia, Louis-Bar syndrome, cortical and vestibular ataxias. In this group, Friedreich's ataxia is the most common disease. Its prevalence worldwide is 2-7 cases per 100 thousand population. Representatives of the Negroid race do not have Friedreich's ataxia.

Friedreich's ataxia is accompanied by damage not only to the nervous system, but also to extraneural disorders. Pathological changes occur in the heart, the organ of vision, the endocrine system and the musculoskeletal system. For this reason, Friedreich's ataxia is of interest to specialists in various fields of medicine: neurology, cardiology, ophthalmology, endocrinology, orthopedics and traumatology.

Causes of Friedreich's ataxia

Friedreich's ataxia is a genetic disease and is associated with a mutation of the 9th chromosome, as a result of which there is a deficiency or deficiency of the frataxin protein. This protein is responsible for the transport of iron from the mitochondria. Violation of its function leads to the accumulation of a large amount of iron inside the mitochondria and an increase in free radicals inside the cell. The latter have a damaging effect on the cell. In this case, the most active cells of the body suffer: neurons (nerve cells), myocardiocytes (heart muscle cells), insulin-synthesizing β - pancreatic cells, retinal receptor cells (rods and cones) and bone tissue cells. The defeat of these cells leads to the development of symptoms characteristic of Friedreich's ataxia from the peripheral and central nervous system, diabetes mellitus, cardiomyopathy, visual impairment, bone deformities.

Friedreich's ataxia is inherited in an autosomal recessive manner. The carrier of the gene mutation that causes it, according to some sources, is 1 out of 120 people. But Fredreich's ataxia develops only if a person inherits a distorted gene from both his father and mother. At the same time, his parents are only carriers of a genetic disorder and do not themselves suffer from Fredreich's ataxia.

Symptoms of Friedreich's ataxia

As a rule, Friedreich's ataxia begins to appear in the first two decades of life. In much rarer cases, signs of the disease appear in the third or fourth decade. Friedreich's ataxia usually develops before the age of 25. It begins with neurological disorders and is characterized by the steady progression of the pathological process with the aggravation of its clinical manifestations.

Friedreich's ataxia debuts with gait and balance disorders. During this period, patients note the appearance of unsteadiness and uncertainty while walking. Their gait becomes awkward, accompanied by frequent trips and falls. Then there is a violation of coordination during movements of the hands, the appearance of a tremor of the hands and the associated change in handwriting. Gradually, weakness in the legs, speech disorders (dysarthria) and hearing loss (hearing loss) join. The speech of patients with Friedreich's ataxia becomes slow and slurred.

In the neurological status in Friedreich's ataxia, the cerebellar and sensitive nature of ataxia is noted. The patient is unstable in the Romberg position, cannot perform the heel-knee test, misses the finger-to-nose test. The results of the tests deteriorate when they are performed with closed eyes, since vision partially compensates for the lack of coordination. An early sign of Friedreich's ataxia is the disappearance of the Achilles and knee reflexes. The presence of Babinsky's symptom is characteristic - extension of the big toe with irritation of the outer edge of the sole. Sometimes the extension of the thumb is accompanied by a fan-shaped divergence of the remaining toes. Babinsky's symptom indicates a lesion of the pyramidal pathway responsible for motor activity.

With the progression of Friedreich's ataxia, total areflexia is noted - the absence of all periosteal and tendon reflexes, a disorder of deep types of sensitivity (vibration sensitivity and joint-muscular feeling), a decrease in muscle tone, weakness (paresis) and atrophic changes in the muscles of the distal (located further from the body) lower parts limbs. In the late stage of Friedreich's ataxia, paresis, muscle hypotension and atrophy extend to the upper limbs. In this case, patients lose the ability to self-service. Perhaps the appearance of pelvic disorders and the development of dementia (dementia). In some cases, Friedreich's ataxia is accompanied by hearing loss, nystagmus, and atrophy of the optic nerves.

Of the extraneural clinical symptoms that manifest Friedreich's ataxia, in 90% of cases there is a lesion of the heart muscle - cardiomyopathy, leading to arrhythmia (extrasystole, paroxysmal tachycardia, atrial fibrillation) and heart failure. Friedreich's ataxia is also characterized by various bone deformities. The most typical is the Friedreich foot, which has an excessively high and concave arch, bent distal phalanges of the fingers and unbent main phalanges. Scoliosis, clubfoot, deformities of the fingers and toes are also noted. On the part of the endocrine system, Friedreich's ataxia is often accompanied by diabetes mellitus, infantilism, hypogonadism, and ovarian dysfunction. In some cases, patients with Friedreich's ataxia have cataracts.

Diagnosis of Friedreich's ataxia

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 an orthopedist for scoliosis. Only with the development of neurological symptoms do they get a consultation with a neurologist.

The main methods of instrumental diagnosis of Friedreich's ataxia are magnetic resonance imaging and neurophysiological testing. MRI of the brain reveals atrophic processes in the medulla oblongata and pons, cerebellar atrophy. An MRI of the spine shows a decrease in the diameter of the spinal cord and its atrophic changes. In the diagnosis of Friedreich's ataxia, CT of the brain is not sufficiently informative. With its help, characteristic changes can be visualized only in the later stages of the disease. Early Friedreich's ataxia is accompanied only by CT signs of mild cerebellar atrophy.

The study of the pathways is carried out using transcranial magnetic stimulation, the study of peripheral nerves - by electroneurography and electromyography. At the same time, Friedreich's ataxia is characterized by a moderate decrease in action potentials during conduction along motor nerves in combination with a large (up to complete disappearance) decrease in conduction along sensory fibers.

Due to the presence of extraneural manifestations, Fredreich's ataxia requires additional studies of the cardiovascular, endocrine, and musculoskeletal systems. For this purpose, a cardiologist, orthopedist, ophthalmologist and endocrinologist are consulted; blood sugar analysis and glucose tolerance test, hormonal studies; ECG, stress tests, multiple sclerosis.

Treatment of Friedreich's ataxia

Adequate and regular treatment of Friedreich's ataxia allows you to stop the progression of the disease, avoid complications, and maintain the patient's ability to lead an active lifestyle for a long time. As a rule, Friedreich's ataxia is treated with the simultaneous administration of metabolic drugs belonging to 3 different groups: cofactors of energy enzyme reactions, stimulators of the activity of the mitochondrial respiratory chain and antioxidants.

Additionally, with Friedreich's ataxia, medications are prescribed that improve metabolic processes in the heart muscle (thiamine pyrophosphate, inosine, trimetazidine, 5-hydroxyprofan, etc.), nootropics and neuroprotectors (gamma-aminobutyric acid, piracetam, meclofenoxate, pyritinol), multivitamins. If necessary, botulinum toxin is injected into the affected muscles, and surgical operations are performed to correct bone deformities.

Physiotherapy exercises are of great importance for patients with Friedreich's ataxia. Constant physical therapy exercises aimed at training coordination and muscle strength make it possible to maintain motor activity and stop the resulting pain. Since Friedreich's ataxia is accompanied by a violation of energy metabolism, patients with this disease need to limit the intake of carbohydrates with food, the excess of which can provoke an aggravation of metabolic disorders.

Friedreich's ataxia prognosis

Friedreich's ataxia has a steadily progressive course, leading to death. The patient dies from heart or respiratory failure, infectious complications. About 50% of patients who have Friedreich's ataxia do not live past the age of 35. In women, the course of the disease is more favorable. Their life expectancy in 100% is 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.

Friedreich's ataxia is a hereditary neurodegenerative disease characterized by impaired excretion of iron ions from the perimitochondrial space of the cell.

Among Europeans, the prevalence of the disease is 1:20,000-1:50,000, and worldwide, every 120th inhabitant has a predisposition to this pathology. The cause of Friedreich's ataxia is a mutation in the FXN gene, in particular, an unstable increase in GAA triplets. This gene encodes a specific protein frataxin, which is responsible for the transport of iron ions from the perimitochondrial space and thereby prevents the formation of free radicals, which have a pronounced damaging effect on the central and peripheral nervous system, as well as other organs.

Friedreich's ataxia is inherited in an autosomal recessive manner. Asymptomatic carriage of the gene is possible.

Clinical manifestations

Mutations in the FXN gene do not immediately lead to a pronounced clinical manifestation of Friedreich's ataxia. The disease may not make itself felt for decades. Usually the first signs occur at a young age - 20-25 years, less often at 30 and 40 years. The debut of the disease begins with disorders of gait and coordination of movements. The patient complains of uncertainty, unsteadiness, awkwardness in movements, notes frequent falls. Later, disorders of the movements of the upper limbs, the appearance of tremor, join. Other manifestations of Friedreich's ataxia include:

weakness in the muscles of the legs;
speech disorders;
hearing loss;
disappearance of reflexes;
dysfunction of the ovaries;
paresis and paralysis;
dementia;
diabetes;
hypogonadism;
optic atrophy.

In addition, the disease is accompanied by various disorders of the heart, for example, arrhythmia, in severe cases - heart failure. Often in patients with Friedreich's ataxia, bone deformities are noted.

Diagnosis of Friedreich's ataxia

It can be difficult to make an accurate diagnosis in some cases. The patient can be observed for a long time by a neurologist, cardiologist, orthopedist or other specialists who cannot always suspect Friedreich's ataxia. In order to identify characteristic changes, it is required to undergo a comprehensive examination, the plan of which will include the following methods:

MRI of the brain or spine;
neurophysiological testing;
electroneurography;
electromyography;
magnetic stimulation.

Of great importance in the diagnosis of Friedreich's ataxia is a genetic examination, which can be used to detect a mutation in the FXN gene and reliably confirm the presence of the disease. You can undergo such an examination at the medical genetic center "Genomed".

Treatment Methods

An effective treatment that could eliminate the cause of Friedreich's ataxia has not yet been developed. However, to improve the quality and duration of life, symptomatic therapy can be used, which is always selected individually. To normalize the work of mitochondria, antioxidants, stimulants of the activity of the respiratory chain, and cofactors of enzyme reactions are prescribed. Bone deformities are corrected mainly by surgical methods. Hormones are used to correct endocrine disorders.

In order to slow down the progression of Friedreich's ataxia, exercise therapy can be prescribed, if necessary, prostheses and wheelchairs are selected to help the patient maintain an active lifestyle.

Forecast

Friedreich's ataxia is an incurable progressive disease. The prognosis for a patient's life largely depends on the age at which it developed and the symptoms. In women, the course is more favorable than in men. Complications in the form of diabetes mellitus, heart failure, bronchopneumonia are considered the most dangerous. In the absence of these disorders, patients can live up to 70 years or more, otherwise life expectancy is limited to 20 years from the onset of disease progression.

Friedreich's ataxia - a hereditary disease of the nervous system, an autosomal recessive type of inheritance. The disease is characterized by a syndrome of damage to the posterior and lateral cords of the spinal cord, more often in the lumbosacral segments, the death of cells of Clark's pillars and dorsal spinocerebellar tracts.

In the later stages, degeneration of the nuclei of the cranial nerves, the dentate nucleus, and the cerebellar peduncle is characteristic, and the cells of the cerebral hemispheres suffer somewhat less frequently.

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 a deficiency or distortion of the structure of a protein synthesized in the cytoplasm - frataxin . This protein is responsible for the transport of iron from mitochondria, with the accumulation of which above the norm, a decrease in cytotic iron occurs.

These are the main causes of the development of Friedreich's ataxia, as a result of which the genes encoding ferroxidase and permease , which, like frataxin, are responsible for the transport of iron.
This leads to even greater accumulation in the mitochondria. Heredity is due to the so-called Friedreich's disease gene, presumably found in the centomeric region of the 9th chromosome at the locus 9ql3 - q21. Several may occur one gene than, and different forms of the disease are caused. Friedreich's ataxia occupies half of the cases of ataxia. The first signs appear before the age of 20, much less often up to 30. It occurs equally often in both women and men, only representatives of the Negroid race are not exposed to this disease

The disease affects the neurons of the central and peripheral nervous system, but medicine has no explanation, the reason why only the pathways of the spinal cord are damaged in the nervous system. In other systems, no less important organ cells are exposed to the disease, these are myocardial cells, β - cells of the islets of Langerhanz in the pancreas, cells of the retina and bone tissues.

The course of the disease is constantly progressive. If there is no adequate treatment for Friedreich's ataxia, the duration of the disease does not exceed 20 years. And having begun to manifest itself as awkwardness and uncertainty when walking, after a while it completely deprives a person of normal coordination of movements and moving independently. The disease ends in death, 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 the inhibition of the Achilles and knee reflexes. These symptoms appear a few years before the appearance of others, as early manifestations include rheumatic heart disease , which is often treated as a separate disease. So it is not considered that these are symptoms of Friedreich's ataxia before the onset of neurological disorders. Gradual skeletal deformities occur, such as scoliosis, finger and toe deformity, "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 . Violated joint-muscular and vibrational sensitivity, muscle hypotension, Babinsky's symptom. Gradually develops sensitive and, atrophy and weakness of the muscles of the legs.

Extraneural manifestations are manifested in 90% of patients, these are heart lesions, endocrine disorders , . A progressive cardiomyopathy , it can be both hypertrophic and dilated. In this case, there are such symptoms of Friedreich's ataxia as pain in the region of the heart, palpitations, systolic murmurs,. endocrine diseases such as diabetes , hypogonadism , .

The late stage of ataxia is characterized amytrophy and a disorder of deep sensitivity, the disappearance of tendon and periosteal reflexes. That extends to the upper limbs. There is a deep disintegration of motor functions, due to which a person loses the ability to walk and serve himself. Developing kyphoscoliosis with the formation of a hump, deformation of the hands. Of the extraneural manifestations, there may be nystagmus, hearing loss, atrophy of the optic nerves, dysfunction of the pelvic organs,. Progressive in the later stages of the disease is the cause of death in half of the patients, most often due to disorders in the conduction system of the heart. Immediate causes of death also include pulmonary insufficiency 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 the later stages. This is due to the spinal localization of changes, therefore, only a mild degree of cerebellar atrophy 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 can be detected. Early diagnosis of Friedreich's ataxia is made using MRI , which makes it possible to detect atrophy of the spinal cord, and at the advanced stage, and moderately pronounced atrophy of the bridge, cerebellum and medulla oblongata. At the initial stage, an electrophysiological study is necessarily carried out, with such studies, the severity of damage to the sensitivity of the nerves of the limbs is established.

For a complete diagnosis, load tests of glucose tolerance, X-ray examination of the spine are performed. First of all, the diagnosis is aimed at accurately establishing the diagnosis and differentiating the disease from others with similar symptoms. For example, the symptoms of Friedreich's ataxia can be the same as hereditary ataxia with deficiency, Bassen-Kornzweig syndrome, hereditary metabolic diseases such as Krabbe disease and Niemann-Pick disease. Similar symptoms can be with, with the exception of tendon areflexia, muscle hypotension and extraneural manifestations. The presence of remissions and changes in the density of the substance of the brain, which is observed in the diagnosis of multiple sclerosis, is not typical for Friedreich's ataxia.

To differentiate the disease, a number of additional laboratory tests are also prescribed. DNA testing and medical genetic counseling, blood lipid profile, blood smear analysis for vitamin E deficiency and acanthocytes. Treatment of Friedreich's ataxia does not lead to a complete 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 prevention and prescribing of preventive therapy.

Treatment of Friedreich's ataxia

To slow the progression of the disease, 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 the development of hypertrophic cardiomyopathy. Also appointed 5-hydroxypropane , which gives good results, but it requires further research.

In general, treatment is symptomatic, it should eliminate such symptoms of Friedreich's ataxia as diabetes , . There is also surgical correction of the feet and the introduction botulinum toxin into spastic muscles.

And physiotherapy - procedures, without which the treatment of Friedreich's ataxia is most often ineffective. Regular exercise makes it possible to keep the body in good shape and eliminate pain. Patients require social adaptation, as many have to live in a state of complete helplessness. Loss of vision, the ability to move independently, impaired coordination creates psychological disorders that must be eliminated with the help of specialists and the support of loved ones.

Main symptoms:

Friedreich's ataxia is a genetic pathology in which not only the nervous system is affected, but also the development of extraneural disorders. The disease is considered quite common - 2-7 people per 100 thousand of the population live with such a diagnosis.

The disease is genetic, associated with mutations of chromosomes. Clinicians identify several specific conditions for the development of pathology.

Symptoms of the disease are specific - the first signs are considered to be impaired walking and loss of balance. The clinical picture includes speech impairment, cataracts, hearing loss and dementia.

Only a neurologist can make a correct diagnosis based on the results of instrumental examinations. Consultations of experts from different fields of medicine are necessary. It should be noted that the diagnosis can be performed already at the stage of intrauterine development of the fetus.

Treatment is predominantly conservative in nature: it consists of taking medication, dieting, and regular exercise of therapeutic exercises. Surgery is necessary in cases of pronounced bone deformities that reduce the quality of life.

Etiology

Hereditary Friedreich's ataxia occurs against the background of insufficient concentration or violation of the structure of a protein called frataxin, which is produced in the cytoplasm by the intracellular route.

The main function of the substance is the transfer of iron from mitochondria - the energy organelles of the cell. Against the background of specific processes, a large amount of iron accumulates - exceeding the norm by dozens of times, which provokes an increase in the number of aggressive oxidizing agents that damage vital cells.

An auxiliary place in the mechanism of the development of the disease is occupied by a disorder of antioxidant homeostasis - the protection of human cells from harmful active oxygen forms.

Friedreich's ataxia can only be inherited in an autosomal recessive manner. The carrier of the mutation of the 9th chromosome is 1 person out of 120. It is noteworthy that the pathology develops only in cases where the mutant gene is inherited from both the mother and the father. It is worth noting that parents are only carriers of a gene disorder, and they themselves do not get sick.

A similar anomaly belongs to the group of ataxias, in which the following species are located:

Pierre-Marie's ataxia;
Louis-Bar syndrome;
cortical ataxia - provoked by violations of the cerebral cortex, which is responsible for voluntary movements;
vestibular ataxia - associated with damage to the vestibular apparatus, as a result of which among the signs of the disease are imbalance, nystagmus, nausea and vomiting, problems with certain movements.

Symptoms

Friedreich's ataxia has a large number of specific clinical signs, which are usually divided into several groups:

typical or neurological;
extraneural;
atypical.

The typical form can manifest before the age of 20, and gender does not become a decisive factor. Experts from the field of neurology note that in women, the period of manifestation of the first symptoms occurs a little later than in men.

gait disturbance and uncertainty while walking;
balance problems;
weakness and fatigue of the lower extremities;
falling for no reason;
the inability to carry out a knee-heel test - a person cannot touch the elbow of his right hand to the knee of his left leg and vice versa;
fuzzy hand movements - tremor of outstretched limbs and change in handwriting;
slurred and slow speech;
decrease or complete loss of tendon reflexes of the legs (knee and Achilles) - in some cases, it occurs several years before the appearance of other signs, later the reflexes are lost on the hands, in particular the flexion-elbow, extensor-elbow and carporadial, and as the disease progresses, it forms total areflexia;
decrease in muscle tone;
a disorder of deep sensitivity - with closed eyes, a person cannot determine the direction of movement of a hand or foot;
paresis and muscle atrophy;
gradual loss of self-service skills;
incontinence or, conversely, urinary retention;
hearing loss;
mental weakness.

Extraneural symptoms:

pain in the region of the heart;
violation of heart rate;
shortness of breath that occurs both after physical activity and at rest;
Friedreich's foot - a high arch is noted, accompanied by hyperextension of the fingers in the main phalanges and flexion in the distal sections;
deformity of the fingers of the upper and lower extremities;
sexual underdevelopment;
the appearance of signs;
weight gain;
in men, feminine features are noted in appearance;
among women.

Atypical Friedreich's ataxia is observed in individuals with a minor mutation of the 9th chromosome. This form of the disease is characterized by a later onset - at 30-50 years. This variety is distinguished by the fact that there are no:

diabetes;
paresis;
heart disorders;
areflexia;
impossibility of self-service.

Such cases are called "late Friedreich's disease" or "Friedreich's ataxia with preserved reflexes."

Diagnostics

Despite the fact that the pathology has specific and pronounced clinical manifestations, in some cases there are problems with establishing the correct diagnosis.

This is especially true in situations where the first signs of the disease are extraneural symptoms - patients are mistakenly observed by a cardiologist or orthopedist for a long period of time and undergo useless diagnostic procedures.

The basis of diagnosis is instrumental examinations, however, the procedures must be preceded by activities performed directly by a neurologist:

studying the family history of the disease;
familiarization with the patient's life history;
assessment of reflexes and appearance of the limbs;
measurement of heart rate;
detailed survey - to establish the first time of occurrence and determine the severity of the clinical picture.

The following instrumental procedures are the most informative:

MRI of the spine and brain;
neurophysiological examinations;
CT and ultrasound;
transcranial magnetic stimulation;
electroneurography;
electromyography;

Laboratory studies are of secondary importance and are limited to a biochemical blood test.

With Friedreich's ataxia, additional consultations of such specialists are required:

cardiologist;
endocrinologist;
orthopedist;
ophthalmologist.

Not the last place in the process of diagnosing is occupied by medical genetic counseling and complex DNA diagnostics. Manipulations are carried out on blood samples of the patient, his parents, siblings.

The course of the disease can be detected even at the stage of pregnancy - Friedreich's family ataxia in the fetus is detected during DNA tests of the chorionic villi, which is performed at 8–12 weeks of gestation or by examining the amniotic fluid at 16–24 weeks of gestation.

It is worth noting that Friedreich's ataxia must be differentiated from such diseases:

funicular myelosis;
neoplasms of the cerebellum;
Louis-Bar syndrome;
hereditary deficiency of vitamin E;
Krabbe disease;

Treatment

Timely initiated therapy makes it possible to:

stop the progression of the pathological process;
prevent the development of complications;
maintain an active lifestyle for a long time.

Drug treatment is based on the simultaneous administration of metabolic drugs from the following groups:

cofactors of energetic enzymatic reactions;
mitochondrial respiratory chain activity stimulators;
antioxidants.

In addition, they prescribe:

nootropic substances;
drugs to improve metabolic processes in the heart muscle;
neuroprotectors;
multivitamin complexes.

Exercise therapy is of great importance - constant therapeutic exercises, compiled on an individual basis, will help:

restore coordination and muscle strength;
maintain physical activity;
eliminate pain.

Treatment involves following a sparing diet, the essence of which is to limit the intake of carbohydrates, since their excess can provoke an aggravation of symptoms.

Surgical intervention is indicated only in cases where a person has pronounced bone deformities.

Possible Complications

Complete lack of therapy can lead to life-threatening complications. Among the consequences, it is worth highlighting:

accession of infections;
disability;

Prevention and prognosis

Friedreich's ataxia is a disease caused by gene mutations, so it is impossible to avoid its development. To find out whether a child will be born with a similar pathology, a married couple at the stage of pregnancy planning needs to consult a geneticist and pass DNA tests.

Thanks to the latest technologies for prenatal diagnosis of chromosomal mutations, carriers of a pathological gene have the opportunity to have healthy offspring.

As for the prognosis, the outcome is unfavorable. Friedreich's ataxia leads to death approximately 20 years after the onset of the first clinical symptoms. On average, every second patient with a similar diagnosis does not live up to 35 years.

It is noteworthy that in women the prognosis is more favorable - in 100% of cases they manage to live more than 20 years from the onset of the pathology, while in men the figure is only 63%.

In the absence of diabetes and heart problems, people can live to an advanced age - up to 70-80 years.

Is everything correct in the article from a medical point of view?

Answer only if you have proven medical knowledge

Friedreich's disease (ATAXIA HEREDITARIA) - the most common form of hereditary ataxia, the prevalence is 2 - 7 per 100,000 population. The type of inheritance is autosomal recessive. The Friedreich disease gene was mapped to the centomeric region of the 9th chromosome at the 9ql3-q21 locus.

Friedreich's disease is characterized by:
degeneration of the posterior and lateral columns of the spinal cord (especially in the lumbosacral segments)
death of cells of Clark's pillars and dorsal spinocerebellar tracts starting from them
degeneration of nuclei III, V, IX-X, XII pairs of cranial nerves, Purkinje cells, dentate nucleus and superior cerebellar peduncle (usually in the late stage of the disease)
changes can also be found in the cerebral hemispheres

Causes of Friedreich's ataxia
The development of the disease is associated with a deficiency or a distorted structure of the frataxin protein, which is synthesized inside the cell in the cytoplasm, its function is the transport of iron from mitochondria. Mitochondria are the "energy stations of the cell", the accumulation of iron in them (iron oxidation is a universal mechanism for transporting oxygen in the body) is associated with a high activity of oxidative processes inside them. With an increase in the iron content in mitochondria by more than 10 times, the total cellular iron remains within the normal range, 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. A high concentration of iron in mitochondria leads to an increase in the number of free radicals, which have a damaging effect on the cell.

The criteria for the diagnosis of Friedreich's disease are:
1.autosomal recessive type of inheritance
2. debut in adolescence, less often in adolescence
3. ataxia, areflexia, violation of deep sensitivity, weakness and atrophy of the muscles of the legs, later than the hands
4. extraneural symptoms:
skeletal deformities: scoliosis, hollow foot (“Friedreich’s foot”), deformity of the toes and hands, etc.
endocrine disorders: diabetes mellitus, hypogonadism, infantilism, ovarian dysfunction
cardiomyopathy (hypertrophic, less often dilated): ECG and EchoCG changes
cataract
1. atrophy of the spinal cord, visualized on MRI scans
2.DNA diagnostics

It is assumed that the classical and atypical forms of Friedreich's disease can be caused by different (two or more) mutations of the same gene.

The first symptoms of the disease occur most often in the prepubertal period. They are characterized by a combination of:
typical neurological manifestations
extraneural manifestations

Neurological manifestations

The disease usually manifests itself by the appearance of awkwardness, uncertainty when walking, especially in the dark, patients begin to stagger, often stumble. Soon, discoordination in the hands, a change in handwriting, and weakness in yoga join the ataxia when walking. Already at the very beginning of the disease, dysarthria may be noted.

Early and an important differential diagnostic sign of Friedreich's disease is the disappearance of tendon and periosteal reflexes.

Inhibition of reflexes (primarily Achilles and knee reflexes) can be several years ahead of the manifestation of other symptoms of the disease and be the earliest manifestation of neurological dysfunction.

In advanced stage diseases in patients with total areflexia is usually observed.

A typical neurological manifestation of Friedreich's disease is a violation of deep (articular-muscular and vibrational) sensitivity.

Quite early in patients with a neurological examination, Babinski's symptom, muscle hypotension, can be detected.

As the disease progresses, cerebellar and sensitive ataxia, weakness and atrophy of the leg muscles gradually increase.

Late stage diseases are frequent, amyotrophies and disorders of deep sensitivity that extend to the hands. Patients cease to walk independently and serve themselves due to the deep decay of motor functions.

In some cases, there is nystagmus, hearing loss, atrophy of the optic nerves; with a long course of the disease, there is a violation of the function of the pelvic organs, dementia.

Extraneural manifestations

Heart failure(occurs in more than 90% of patients)
Characteristic is the development of a typical progressive cardiomyopathy.
Cardiomyopathy is predominantly hypertrophic, but in some cases dilated cardiomyopathy may develop. It is possible that these heart changes in Friedreich's disease are different stages of the same process.
Cardiomyopathy manifests itself:
pain in the region of the heart
heartbeat
shortness of breath on exertion
systolic murmur and other symptoms.

In more than half of patients, cardiomyopathy is the direct cause of death.

Relevant changes are usually detected:
on the ECG - rhythm disturbance, T-wave inversion, conduction changes
with echocardiography

In some cases, clinical and electrocardiographic symptoms of heart damage sometimes precede the appearance of neurological disorders by several years. Patients are observed for a long time by a cardiologist or a local therapist, most often with a diagnosis of rheumatic heart disease.

Skeletal deformities:
scoliosis
“Friedreich’s foot” - a high concave arch of the foot with hyperextension of the fingers in the main phalanges and flexion in the distal
deformity of the fingers and toes, etc.

These disorders can also appear long before the first neurological symptoms develop.

Endocrine Disorders:
diabetes
hypogonadism
infantilism
ovarian dysfunction

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 can be heart and lung failure, infectious complications.

Additional diagnostic methods

1. MR imaging- allows you to visualize atrophy of the spinal cord already at an early stage of the disease, and with a longer course - a moderately pronounced atrophy of the medulla oblongata, pons and cerebellum.

2. CT scan of the brain is of limited importance (due to the spinal localization of the main morphological changes) - either a weak degree of cerebellar atrophy or no changes are detected.
Only in the late stage of the disease can CT detect a number of changes:
atrophy of the hemispheres and cerebellar vermis
expansion of the IV ventricle, stem cisterns, lateral ventricles and subarachnoid space of the cerebral hemispheres

However, the degree of these changes remains weak or moderate even in the most severe patients. These features of the CT picture in Friedreich's disease make it possible to use it for differential diagnosis with other, primarily cerebellar, forms of hereditary ataxia.

3. Electrophysiological studies(are informative for the diagnosis of Friedreich's disease)

The electroneuromyographic pattern characteristic of this disease is in the absence or significant decrease in the amplitude of the action potentials of the sensory nerves of the extremities, with a relatively small decrease in the speed of impulse conduction along the motor nerves.

Even in the initial stage of Friedreich's disease, it is necessary to use electrocardiography and echocardiography, examine the blood glucose level with special glucose tolerance stress tests (to rule out diabetes mellitus), and also conduct an X-ray examination of the spine (characteristic of bone deformities).

Differential Diagnosis

Friedreich's disease must be differentiated from:

hereditary ataxia caused by deficiency vitamin A E(for differential diagnosis, it is necessary to determine the content of vitamin E in the blood, examine the lipid profile of the blood, blood smear for the presence of acanthocytosis)

Bassen-Kornzweig syndrome

metabolic diseases inherited in an autosomal recessive manner and often characterized by the development of spinocerebellar ataxia - Gm 1 and Gm 2 - gangliosidosis and galactosialidosis(study of the activity of β-galactosidase and hexosaminidase A), Krabbe disease (study of the enzyme galactosylceramidase), late version Niemann-Pick disease(determination of the content of sphingomyelins in cerebrospinal fluid, examination of sternal punctate for the presence of “foamy” cells).

multiple sclerosis(differential diagnosis usually does not cause difficulties, since symptoms such as tendon areflexia, muscular hypotension, amyotrophies, extraneural manifestations are not typical for multiple sclerosis, and also due to the absence of remissions and focal changes in the density of the brain substance in CT and MR imaging in Friedreich's disease )

Treatment of Friedreich's ataxia

There is no cure leading to complete recovery.

Preparations of the so-called mitochondrial series, antioxidants and compounds that help reduce the accumulation of iron in mitochondria are used.

Among 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.

Observation of an endocrinologist, orthopedic correction of the feet (Friedreich's foot) is necessary.

It is also of great importance physiotherapy and physiotherapy.

In some cases, there are foot deformity surgery, introduction botulinum toxin into spastic muscles.

Patients need social adaptation.

Prevention of Friedreich's ataxia

Of particular importance is DNA testing at an early presymptomatic stage in order to prescribe preventive therapy. First of all, the relatives of the patient are examined.