Friedreich's ataxia
Friedreich's ataxia is a hereditary and neurodegenerative disease that affects young people and is characterized by a slowly progressive deterioration of gait coordination and the ability to maintain correct body posture, as well as other neurological signs and symptoms. It is the most common hereditary ataxia with an autosomal recessive pattern of inheritance.
The disease causes in those who suffer from it a progressive deterioration of the cerebellum and dorsal spinal ganglia. This degeneration unstoppably causes those affected to progressively lose many of the functions necessary for personal autonomy: loss of sensitivity, incoordination in movements, scoliosis, dysphagia, dysarthria, immunodeficiency, radiosensitivity (sensitivity to radiant energy, like that of an x-ray), and predisposition to cancer and in many cases diabetes and serious heart problems, causing death in most cases.
Those affected by this disease, in a more or less short time, are forced to use a wheelchair and, progressively, each day more, to depend on the attention and care of their relatives, because they end up losing all autonomy staff.
Friedreich's ataxia was described by the German neurologist Nikolaus Friedreich, and in 1988 it was possible to identify the mutation of the responsible gene and its location on chromosome 9. For this reason, from the year 2000, the international day of ataxia, which is celebrated on September 25 of each year, with the aim of making the population aware of this rare disease and donating assets to improve the quality of life of these patients.
Causes
Friedreich's ataxia is an autosomal recessive disease, which means that the patient must inherit two affected genes, one from each parent, for the disease to develop. A person who has only one abnormal copy of a gene for a recessive genetic disease, such as Friedreich's ataxia, is called a carrier. A carrier will not get the disease but could pass the affected gene on to her children. If both parents carry the gene for Friedreich's ataxia, their children will have a 25% chance of developing the disease and a 50% chance of inheriting an abnormal gene that they, in turn, could pass on to their children.
About one in 90 European Americans carry the affected gene. Human beings have two copies of each gene: one inherited from the mother and one from the father. Genes are located at specific locations on each of an individual's 46 chromosomes, which are tightly coiled strands of DNA that contain millions of chemicals called bases. These bases—adenine, thymine, cytosine, and guanine—are called A, T, C, and G for short. Certain bases always pair (A with T; C with G), and different combinations of base pairs come together in sets of three to form coded messages. These coded messages are "recipes" for making proteins.
By combining into long sequences, like long phone numbers, paired bases tell each cell how to assemble different proteins. Proteins make up the specialized cells, tissues, and enzymes that our bodies need to function normally. The protein that is altered in Friedreich's ataxia is called frataxin. In 1996, an international group of scientists identified the cause of Friedreich's ataxia as a defect in a gene located on chromosome 9.
Due to abnormal inherited code, a particular sequence of bases (GAA) is repeated too many times. Normally, the GAA sequence repeats 7 to 22 times, but in people with Friedreich's ataxia, it repeats 800 to 1,000 times. This type of abnormality is called "triple repeat expansion" and has been identified as the cause of several dominantly inherited diseases.
Friedreich's ataxia is the first recessive genetic disease known to be caused by triplet repeat expansion. Although 98 percent of Friedreich's ataxia carriers have a particular genetic triple expansion repeat, it is not found in all cases of the disease. A very small proportion of affected people have other genetic coding defects that are responsible for the disease. The triple expansion repeat apparently disturbs the normal conversion of amino acids to protein, greatly reducing the amount of frataxin that is produced.
Research indicates that without a normal level of frataxin, certain cells in the body (particularly brain, spinal cord, and muscle cells) cannot withstand the normal amounts of "oxidative stress" produced by frataxin. mitochondria, the power plants of cells. This indication of the possible cause of Friedreich's ataxia was discovered after scientists carried out studies using a yeast protein with a similar structure to human frataxin. They found that the lack of this protein in the yeast cell led to a toxic concentration of iron in the cell's mitochondria. When excess iron reacted with oxygen, free radicals were produced. Although free radicals are essential molecules in the body's metabolism, they can also destroy cells and cause damage to the body.
Clinical picture
Symptoms commonly begin between ages 5 and 15, but may rarely appear as early as 18 months or as late as 30 years of age. The first symptom to appear is usually difficulty walking or gait ataxia. The ataxia gradually worsens and slowly spreads to the arms and then to the trunk. Early signs include foot deformities such as claw foot, toe flexion (involuntary toe flexing movements), big hammer toes, and inversion of the feet (flexion of the feet). into). Over time, muscles begin to weaken and atrophy, especially in the feet, lower legs, and hands, and deformities develop.
Other symptoms include loss of tendon reflexes, especially in the knees and in the wrists and ankles. There is often a gradual loss of sensation in the extremities, which may spread to other parts of the body. Dysarthria (slow diction or indistinct diction) appears and the person tires easily. Rhythmic, rapid, and involuntary movements of the eyeball are common. Most people with Friedreich's ataxia develop scoliosis (curving of the spine to one side) which, if acute, can make it difficult to breathe.
Other symptoms that may occur include chest pain, shortness of breath, and heart palpitations. These symptoms are the result of different forms of heart disease that often accompany Friedreich's ataxia, such as cardiomyopathy (lengthening of the heart), myocarditis (inflammation of the heart wall), myocardial fibrosis (formation of heart-like material), to fibers in the heart muscles) and heart failure.
Rhythmic abnormalities of the heart such as tachycardia (rapid heartbeat) and heart block (impaired conduction of cardiac impulses within the heart) are also common. Approximately 20 percent of people with Friedreich's ataxia develop carbohydrate intolerance, and 10 percent of these develop diabetes mellitus. Some people lose the ability to hear or see. The way the disease progresses varies from person to person. Typically, within 15 to 20 years after the first symptoms appear, the person is confined to a wheelchair, and in later stages of the disease, people become totally disabled. Life expectancy is greatly affected, and most people with Friedreich's ataxia die in early adulthood if there is also serious heart disease, the most common cause of death. However, some people with less severe symptoms of Friedreich's ataxia live much longer.
Diagnosis
Doctors diagnose Friedreich's ataxia by performing a careful clinical exam, including a medical history and a thorough physical exam. Tests that may be done include the following:
- Electromyogram (EMG), which measures the electrical activity of muscle cells.
- Nerve driving study, which measures the speed at which nerves transmit impulses.
- Electrocardiogram (ECG), which gives a graphic presentation of the electrical activity or pulse pattern of the heart.
- Ecocardiogram, which records the position and motion of the heart muscle.
- Magnetic resonance imaging (MRI) scans or computed tomography (CT), which provides an image of the brain and spinal cord.
- Spinal derivation or puncture to evaluate the brain spinal fluid.
- Blood and urine tests to evaluate high levels of glucose.
- Genetic tests to identify the affected gene.
Treatment
Like many degenerative diseases of the nervous system, there is currently no effective cure or treatment for Friedreich's ataxia. However, many of the symptoms and complications associated with this disease can be treated in order to help patients maintain optimal function for as long as possible. Diabetes, if present, can be treated with diet and medications such as insulin, and some heart problems can be treated with medications as well. Orthopedic problems such as foot deformities and scoliosis can be treated with braces or surgery. Physical therapy can prolong the use of the arms and legs. Scientists hope that recent advances in understanding the genetics associated with Friedreich's ataxia may lead to momentous advances in treatment.