Friedreich’s ataxia is a genetic disease associated with impaired transport of iron from mitochondria and occurs with a predominant lesion of cells of the central and peripheral nervous system, cardiomyocytes, beta cells of the pancreas, bone tissue cells and retina. Friedreich’s ataxia is diagnosed using MRI of the brain and spinal cord, neurophysiological studies, and genetic diagnostics. Additionally, an ECG, ultrasound of the heart, hormonal background examination, radiography 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.
G11.1 Early cerebellar ataxia
Friedreich’s ataxia was described in 1860 by a German doctor, whose name the disease still bears. Friedreich’s ataxia belongs to the group of ataxias, which also includes cerebellar ataxia, Pierre-Marie ataxia, Louis-Bar syndrome, cortical and vestibular ataxia. Disease is the most common disease in this group. 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 by 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.
Pathology is a genetic disease and is associated with a mutation of the 9th chromosome, as a result of which there is a deficiency or inferiority of the frataxin protein. This protein is responsible for the transport of iron from 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. At the same time, the most active cells of the body suffer: neurons (nerve cells), myocardiocytes (heart muscle cells), insulin-synthesizing beta cells of the pancreas, retinal receptor cells (rods and cones) and bone 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 disturbances, bone deformities.
Disease is inherited in an autosomal recessive way. The carrier of the gene mutation causing it, according to some data, is 1 person out of 120. But Fredreich’s ataxia develops only if a person inherits a distorted gene from both father and mother. At the same time, his parents are only carriers of a genetic disorder and do not suffer from Fredreich’s ataxia themselves.
As a rule, Friedreich’s ataxia begins to manifest itself in the first two decades of life. In much rarer cases, there are signs of the disease 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 a steady progression of the pathological process with an aggravation of its clinical manifestations.
Friedreich’s ataxia debuts with walking and balance disorders. During this period, patients note the appearance of shakiness and uncertainty while walking. Their gait becomes awkward, accompanied by frequent stumbles and falls. Then there is a violation of coordination during hand movements, the appearance of tremor of the hands and the associated changes in handwriting. Gradually, weakness in the legs, speech disorders (dysarthria) and hearing loss (hearing loss) are added. The speech of patients with Friedreich’s ataxia becomes slow and slurred.
In the neurological status of Friedreich’s ataxia, the cerebellar and sensetive nature of ataxia is noted. The patient is unstable in the Romberg pose, cannot perform a heel-knee test, misses when performing a finger-nasal 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 achilles and knee reflexes. It is characterized by the presence of Babinsky’s symptom — 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 divergence of the remaining toes. Babinsky’s symptom indicates a lesion of the pyramidal pathway responsible for motor activity.
With the progression, total areflexia is noted — the absence of all periosteal and tendon reflexes, a disorder of deep types of sensitivity (vibration sensitivity and articular-muscular feeling), a decrease in muscle tone, weakness (paresis) and atrophic changes in the muscles of the distal (located further from the body) parts of the lower extremities. In the late stage of Friedreich’s ataxia, paresis, muscular hypotension and atrophy spread to the upper extremities. At the same time, patients lose the ability to self-care. The appearance of pelvic disorders and the development of dementia (dementia) is possible. In some cases, Friedreich’s ataxia is accompanied by hearing loss, nystagmus, and optic nerve atrophy.
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’s foot”, which has an excessively high and concave arch, bent distal phalanges of the fingers and unbent main phalanges. There is also scoliosis, clubfoot, deformities of the fingers and toes. 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 have cataract.
Diagnosis of the disease is most difficult in cases where Friedreich’s ataxia begins with extraneural manifestations. At the same time, some patients have been observed for several years by a cardiologist for heart disease or by 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 are magnetic resonance imaging and neurophysiological testing. Brain MRI reveals atrophic processes in the medulla oblongata and bridge, cerebellar atrophy. MRI spine shows a decrease in the diameter of the spinal cord and its atrophic changes. In the diagnosis of Friedreich’s ataxia, a CT brain is not informative enough. With its help, characteristic changes can be visualized only in the later stages of the disease. Friedreich’s early ataxia is accompanied only by CT signs of minor cerebellar atrophy.
The study of the pathways is carried out using transcranial magnetic stimulation, the study of peripheral nerves is carried out by electroneurography and electromyography. At the same time, Friedreich’s ataxia is characterized by a moderate decrease in action potentials when conducted along motor nerves in combination with a large (up to complete disappearance) decrease in conductivity along sensitive fibers.
Due to the presence of extraneural manifestations, disease requires additional studies of the cardiovascular, endocrine and musculoskeletal systems. For this purpose, a consultation of a cardiologist, orthopedist, ophthalmologist and endocrinologist is carried out; blood sugar analysis and glucose-tolerance test, hormonal background study; ECG, stress tests, ultrasound of the heart; spine x-ray.
Of no small importance in establishing the diagnosis of “Friedreich’s ataxia” is medical and genetic counseling and comprehensive (direct and indirect) DNA diagnostics. It is performed on blood samples of the patient, his biological parents, as well as 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, Crabbe disease, Louis-Bar syndrome, hereditary vitamin E deficiency), multiple sclerosis.
Adequate and regular treatment makes it possible 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 simultaneous administration of metabolic drugs belonging to 3 different groups: cofactors of energy enzyme reactions, stimulators of mitochondrial respiratory chain activity and antioxidants.
Additionally, Friedreich’s ataxia prescribes medications 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, surgical operations are performed to correct bone deformities.
Physical therapy is of great importance for patients with Friedreich’s ataxia. Constant physical therapy classes aimed at training coordination and muscle strength, make it possible to maintain motor activity and stop the painful sensations that arise. 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, an excess of which can provoke an aggravation of metabolic disorders.
Friedreich’s ataxia has a steadily progressive course, leading to a fatal outcome. The patient dies from cardiac or respiratory failure, infectious complications. About 50% of patients with Friedreich’s ataxia do not live to 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 cardiac disorders and diabetes mellitus, patients live up to 70-80 years.