Friedreich ataxia: symptoms, diagnosis, treatment

Friedreich's ataxia is a hereditary disease characterized by a violation of the transmembrane iron transport and the most energy-dependent cells of the body: neurons, cardiomyocytes, pancreatic cells, retinal cells and the musculoskeletal system. In this article I will tell you about the symptoms of this illness, about the diagnosis and possible treatment of the disease.

Among the hereditary ataxias this species is most often found: in 2-7 people per 10, 00 people diagnose this pathology. Manifestations of the disease can be detected by a wide variety of specialists: neuropathologists, cardiologists, orthopedists, oculists, endocrinologists. Molecular DNA testing plays a major role in the diagnosis of Friedreich disease. In the treatment of this pathology, there is still no point, the solution lies within the limits of molecular genetics. There is an interesting feature: representatives of the Negroid race are not subject to Friedreich's ataxia.

Causes

Violation of the synthesis of frataxin leads to excessive accumulation of iron and damage to nerve cells.

The disease is autosomal recessive. This means that the development of the disease occurs in the event that both the father and mother are carriers of the pathological gene. The mutation is located in the long arm of the 9th chromosome, resulting in the breakdown of the synthesis of the frataxin protein. This leads to an increase in the iron content within the mitochondria. A high concentration of iron promotes the formation of free radicals that destroy the structure of the cell. The most sensitive to damage are cells of the nervous system (mainly the posterior and lateral columns of the spinal cord, spinal cord tracts, sensitive fibers of peripheral nerves), myocardiocytes, pancreatic β-insulin apparatus, sticks and cones of the retina, cells of the bone system.

Depending on the severity of the genetic defect, there can be both "classical" forms of the disease (with a pronounced mutation) and atypical, relatively benign syndromes.

Symptoms

Before the advent of DNA diagnostics, the clinical manifestations of Friedreich's ataxia were described only in the so-called "classical" form. After the introduction of DNA analysis, it became clear to scientists that the true prevalence of the disease is much higher than previously thought. They began to distinguish and erased, atypical forms.

Typical Friedreich ataxia

The disease often debuts with violations of gait and balance, while the patient is unstable in the Romberg position.

Begins at the age of 10-20 years. The disease is characterized by steady progression and an increase in symptoms. Women live a little longer, although they are subject to this pathology on a par with men. The following neurological manifestations of the disease are distinguished:

• Disturbance of walking and balance: at first there appears uncertainty when walking, more pronounced at dusk and at night. Gradually, staggers, stumbling on walking and even unmotivated falls join. The patient is unstable in the Romberg position, can not perform a knee-heel test (touch the opposite knee with an elbow);
• Violation of coordination in the hands, which is accompanied by a miss when carrying out the finger test, tremor of outstretched arms, violation of handwriting;
• Uneven speech, or dysarthria;
• One of the earliest symptoms is a decrease (or loss) of tendon reflexes from the lower extremities: knee and achill. Sometimes this symptom appears a few years before the onset of other neurological disorders. With the progression of the disease, reflexes of the upper limbs are also lost: flexor-ulnar, extensor-elbow, carporadial. A total areflexia develops;
• Violation of deep sensitivity: vibration and joint-muscle feelings. With closed eyes, disorders in Romberg's posture intensify, the patient can not determine the direction of passive movement limb (for example, when the patient's eyes are closed, the doctor flexes or unbends any finger of the hand or foot. A patient with Friedreich's ataxia can not determine which finger the doctor took and in which direction the movement is being made);
• Decreased muscle tone;
• In far-reaching stages, paresis (weakness) and muscle atrophy develop. Weakness extends from the lower limbs to the upper limbs. Gradually lost self-service skills;
• Possible disorders of the pelvic organs (urinary incontinence or retention);
• Sometimes symptoms of brain damage join: nystagmus (eyelid tremor), hearing impairment, mental weakness, optic nerve atrophy.

Extra-neural manifestations of the disease:

• Cardiomyopathy (hypertrophic or dilated) - accompanied by pain in the heart, palpitation, heart rhythm disturbance, dyspnea. Sometimes patients first turn to the cardiologist only in this regard, since the other symptoms of Friedreich's disease are absent. Progression of cardiomyopathy leads to heart failure, from which patients die;
• Bony deformities - kyphoscoliosis is possible, deformations of the fingers and toes, clubfoot. Characteristic is the "Friedreich's foot" - a high arch with an overextension of the fingers in the main phalanges and bending in the distal ones;
• Endocrine manifestations - diabetes, obesity, sexual underdevelopment (infantilism), dysfunction of the ovaries;
• Cataract.

Most patients have many of the above symptoms. Usually, from the time of the initial manifestations of ataxia and to the lethal outcome, a little over 20 years pass. The cause of death is pulmonary or cardiac failure, the infectious complications that have joined.

Atypical forms

Developed in people with a minor mutation in the 9th chromosome. Characteristic of the later age of the onset of the disease is 3-5 decades of life. The course and prognosis for life are more favorable than in the "classical" form of Friedreich's ataxia.

Atypical forms there is no areflexia, cardiomyopathy, diabetes mellitus. Pareses do not develop, for a long time the ability to self-service persists. Such cases are described under the name "late Friedreich disease", "Friedreich's disease with preserved reflexes".

Diagnostics

An accurate diagnosis is established by polymerase chain reaction.

To confirm the diagnosis of Friedreich's ataxia, the physician takes into account the autosomal recessive type of inheritance, the debut in adolescence or adolescence, the combination of ataxia with areflexia, a violation of deep sensitivity, weakness and atrophy of the muscles of the legs and arms, skeletal deformities, endocrine disorders and cardiomyopathy.

Of the additional diagnostic methods used:

• MRI (magnetic resonance imaging) - even at early stages, diffuse atrophy of the spinal cord is detected, a little later it is possible to identify cerebellar atrophy;
• electroneuromyography - a moderate decrease in the action potential on motor fibers is shown, expressed by (down to complete disappearance) reduction in the action potential along sensitive conductors;
• ECG, ultrasound of the heart, stress tests - for diagnosis of heart disease;
• a blood sugar test and an assessment of glucose tolerance - to identify underlying diabetes mellitus;
• radiography of the spine;
• for reliable confirmation of the diagnosis, DNA diagnostics is used - blood samples are subjected to a polymerase chain reaction and a mutation is detected.

Today, thanks to new technologies, prenatal diagnosis of chromosome mutations has become possible, including Friedreich's ataxia, which allows carriers of pathological genes to have healthy offspring.

Treatment

To date, the therapy of this disease is only symptomatic. Molecular genetics are working on the creation of drugs that will "remove" the mutation or its biochemical consequences.
Among the drugs used:

• antioxidants - vitamin E and A, for the same purpose (as well as with restorative) use of multivitamins;
• synthetic analogue of coenzyme Q10 - (nooben) in order to "slow down" the process of degeneration in the nervous system and to stop the development of cardiomyopathy;
• nootropics - piracetam, aminalon, encephabol, cerebrolysin, cytochrome C, picamilon, semax, ginkgo biloba;
• metabolites - cocarboxylase, riboxin, mildronate, cytoflavin;
• Botulinum toxin - with spasticity of muscles.

Surgical correction of the deformities of the feet and spine is performed. In parallel, the treatment of diabetes mellitus, cardiomyopathy in the endocrinologist and cardiologist. Cataracts undergo surgical treatment with ophthalmologists.
LFK and massage are necessary for patients to maintain motor activity and muscle strength. Sometimes physical therapy allows long time to eliminate pain in the muscles without the use of pain medications.

Educational program on neurology, lecture e. m. Kotova A. FROM. on topic »Ataxia Friedreich»