Here is a description of some forms of recessive autosomic cerebellar ataxias (in other words it is obligatory that the two parents transmit the faulty gene to have a child afflicted by these diseases). Both men and women can be afflicted.
Friedreich’s ataxia is a severe disease which was described for the first time by the German neurologist Nicolas Friedreich in 1881.
The ataxia causes an inability to coordinate the movements of the voluntary muscles (ataxia) attributable to the premature death of the nervous cells which control balance and coordination. With these troubles are associated a thickening and an attack of the functioning of the cardiac muscle (cardiomyopathy) due to the reduced production of a protein, frataxin.
This decrease in frataxin brings an excessive accumulation of iron in the cells, which results in a poor functioning of the mitochondria particularly on the level of the nervous system and the heart. Mitochondria are the structures which generate energy on the cellular level. This poor functioning of the mitochondria is also manifested by an excessive increase of certain products in the blood such as malondialdehyde. (Dr. Michel Vanasse, neurologist, Sainte-Justine Hospital, Montreal).
Mode of transmission : recessive autosomic (affects both sexes and both parents must transmit the gene to have a child afflicted by the disease). The disease, in spite of the fact that it is hereditary, is not always present in each generation.
Age of appearance : The symptoms appear most of the time around 13-14 years of age. Cases are observed in children and in adults. The most recent data inform us that it would be more accurate to say from 1 to 80 years of age.
Symptoms : Friedreich’s ataxia affects the upper and the lower limbs, the muscles of the trunk, the neck and the head. It brings about a loss of the positioning sense of the legs which makes balance become difficult (coordination and precision). At the beginning, there are troubles walking and balancing (similar to a person in a state of intoxication) : little by little, walking becomes unstable with an increasing distance between the feet, inequality of steps, excessive spacing of the lower and upper limbs, the alignment of heels are more or less damage. The person begins to need help to move around.
As the disease progresses, other symptoms can manifest themselves such as a poor coordination of the lower and the upper limbs (clumsiness of the hands from which comes difficulty to write, a generalized muscular weakness (more so in the legs), the loss of certain reflexes, problems of elocution and articulation (difficulty speaking with an explosive and slow voice, irregularity in the tone and the intensity of the voice).
Swallowing is sometimes difficult (the person chokes while swallowing liquids and solids) and, in the majority of cases, there will be a loss of coordination of the ocular muscles (irregular movements of the eyes), and a loss of visual and auditory acuity (deterioration of the visual and auditory nerves). A deformation of the spinal column is also present in a great number of afflicted persons.
Because of the evolution of the disease, from 8 to 10 years following the first sign of symptoms, the afflicted person will have to use a wheelchair in order to palliate his inability to walk.
Secondary problems (not in all cases) :
- Cardiac problems (hypertrophic cardiomyopathy, i.e., the heart is larger than normal and causes anomalies of the rhythm of the cardiac pulse). Important to be followed up regularly.
- Diabetes is sometimes present.
Deformations (not in all cases) :
- hollow feet (the top of the foot will bulge and the bottom in the centre will be hollow)
- spinal column (scoliosis, lordosis, kyphosis), related to incoordination and to posture
Evolution : The evolution is faster at the beginning and the afflicted persons will see themselves confined to a wheelchair. The evolution and the symptoms can be different from one person to another even if these persons belong to the same family.
Cause : One single gene is the cause. Friedreich’s ataxia results from a mutation (alteration or change produced in the gene and preventing it from functioning normally) in the encoding gene for a protein called “frataxin”. Gene X25 was discovered in 1996 on chromosome 9. The function of this gene is to make a protein : frataxin. Its role is to make oxygen circulate through the mitochondria present in each cell. However, in Friedreich’s ataxia, the frataxin is insufficient. Little frataxin being present, oxygen does not circulate in the mitochondria and accumulates at its entrance. Given that the mitochondria need iron to live, right from its arrival, it is oxidized by the accumulated oxygen. The iron rusts and the cell dies.
Diagnostic test : The gene having been discovered, a blood sample is sufficient to know if an individual is healthy, a carrier, or afflicted. An early diagnosis is very important, to detect the different symptoms in order to take charge of them as quickly as possible. A series of tests can be necessary in case of uncertainty:
- molecular biology
- nuclear medicine
- lumbar puncture
- magnetic resonance
Taking charge : Neurological follow-up is indispensable to evaluate the evolution of the disease in order to better orient the patient to the clinical and technical services (taking charge) required. Cardiac and diabetic follow-up may likewise be necessary.
Cardiac problem : gives the seriousness of the disease and the final diagnosis.
Functional reeducation : Reeducation allows one to limit functional losses and to avoid deformations, therefore complications. The goal is to keep a good autonomy if not an improvement. These readaptation services allow them to develop autonomy and to maintain for as long as possible their acquired experience which eases their social integration.
- physiotherapy (all regarding physical upkeep)
- speech therapy (for speech difficulties)
- occupational therapy (aims at autonomy in daily life)
Cure and research : For the moment no cure exists but the symptoms can be treated. For the duration of one year, eleven Friedreich’s ataxics were treated with idebenone.
Mode of transmission : recessive autosomic (affects both sexes and both parents must be carriers of the gene but they are not afflicted).
Age : right from early childhood, when the child starts to walk. Toward the twenties, atrophy of the hands and the feet. Around 30-40 years of age, the person uses a wheelchair to travel long distances.
Frequency : in this region, one person out of 22 is a carrier. There are around 320 afflicted Quebecois.
Evolution : slow and progressive. As the patient grows older, the anomalies in the cerebellum accentuate, limiting coordination and balance. Life expectancy is equal to the population in general.
- lack of balance while walking bringing frequent falls,
- spasticity especially in the legs (accentuating as time goes by),
- lack of coordination of the movements of the arms (from which comes the difficulty to write and to execute precise movements),
- difficulty to pronounce words and a slow, thick, slurred speech,
- progressive weakness (because of the attack on the responsible nerves of the feet and the hands).
Deformation : slight deformation of the feet and the hands.
Secondary problems : none. No cardiac troubles, diabetes or others.
Screening : to be done around 4 years of age.
Functional reeducation : occupational therapy, physiotherapy, and speech therapy in order to limit functional losses and to prevent certain complications. These readaptation services allow them to develop their autonomy and to maintain for as long as possible their skills which facilitate their social integration.
Gene and protein : the gene is discovered and its protein is SACSINE. It has undergone a mutation and consists of an expansion of the CGA trinucleotides. This information is important to know if the patient is ataxic.
Medical research :
- studies on the role and the function of the protein,
- evolution of the disease,
- medication to reduce the spasticity in the legs,
- find a test to identify the disease.
Year of discovery: 2006
Origin of identification: In Quebec, Beauce and Bas-Saint-Laurent regions.
Responsible gene: SYNE 1.
Symptoms: Locomotion problems (balance), dysarthria and manual dexterity difficulties.
Life expectancy: Normal.
Age at onset: About thirty.
Mode of transmission: Recessive. The presence of two abnormal genes is necessary for the disease to manifest itself.
Aid to mobility: Cane to strengthen the support and provide more safety.
Curative treatment: So far there has been no remedy or treatment to cure ataxia of Beauce. Yet, it is possible to treat the symptoms. The functional rehabilitation is necessary. The physiotherapist, the speech-language pathologist (for the diction problems), the occupational therapist (for the assistance with daily living), the psychologist and the social worker work in close collaboration for the evaluation, medical care and support.
The physiotherapist will be very useful for all of your physical movements. The physiotherapist will treat your articulations and muscles. Stretching, strengthening, flexibility will be appropriate to keep your abilities at their current level as long as possible.
Your walk-pattern will also be studied and corrected in order to help you move on your legs more easily. Do you need an orthopedic equipment to facilitate your movements? If yes, which one would be the most suited to your needs? Do you correctly use your cane? Do you have a regular exercise program? Feel free to discuss it with your physiotherapist. The occupational therapist can help you in giving you some helpful tips. She knows all useful objects and gadgets for people who have dexterity problems. She will put you in a difficult position and will find the best way to adapt it to your condition (for example: grab a glass of water and bring it to the table, bring packages etc. Moving some furniture is often enough to make a room more accessible… and a life more pleasant). An external, informed and accustomed eye can be very useful.
The speech-language pathologist can help you normalizing the speed of your voice and its tone. Breathing exercises will be useful to learn how to relax when walking. A small tip to check your voice quality: record yourself and listen to yourself. You will decide then. The psychologist will help you to find a good moral and mental stability. It’s normal to be shocked, depressed and totally disoriented when being diagnosed with ataxia. People don’t want to believe it. Sooner or later, people will have to change their lifestyle and live with ataxia. But it would be better sooner rather than later. There are beautiful moments ahead and your family and friends like you, regardless of your present physical condition. Don’t stay in the questioning phase, consult and find inner harmony.
It is interesting to have the help, opinions and advices of a professional in rehabilitation field. It is useful to have the point of view of another person, reliable and objective to assess the problems and find the treatments and appropriate solutions.
Take a look at the section In everyday life, the lower part concerns you. It’s entitled « How ataxias that appear at adulthood become a reality in the daily life? ».
Here are the scientific research steps to be undertaken:
- Find the cause;
- Know the biological mechanisms
- Create animal models to do clinical trials; thanks to the results of those trials, find a treatment that will hopefully be useful.
Mode of transmission : recessive autosomic (afflicts both sexes and both parents must be carriers of the faulty gene without however being afflicted).
Appearance : starts with the small child and brings about a progressive handicap. The child is normal at birth. The first signs of the disease appear during the second year of life.
- loss of balance,
- elocution difficulty,
- loss of muscular control (confines the patient to a wheelchair),
- loss of writing,
- nystagmus (difficulty in controlling the movement of the eye),
- repeated respiratory infections and progressive neurological damaging,
- accelerated cutaneous-mucous aging,
- particular frequency of certain cancers concerning 10% of the children,
- a vein in the shape of a star appears in the corner of the eye or on the surface of the ears. 70% of the children are clinically noted “immunodeficiency” because of respiratory infections which can be treated life-long.
Cancer : predisposition to cancer. T-A patients are more susceptible to have cancer of the blood, 1000X more than the population in general. Leukaemia and cancer of the lymph are the most common types of cancer. But there is an extreme sensitivity to radiation, therefore the patients do not tolerate it.
Sex and age : men as well as women, all the children are afflicted. 1 case/40,000 births although many have not been diagnosed and are deceased. Nevertheless, this disease is very common.Youths are confined to a wheelchair around the age of 10 years and will die of respiratory problems or from cancer between 10 and 20 years of age. Some will live until 40 years of age but it is extremely rare.
Evolution : progressive.
Gene : on chromosome 11, discovered in 1995.
Diagnosis : in the first stages of the disease, the diagnosis is difficult to give. The characteristics allowing one to affirm the diagnosis is the quasi constant increase of the alpha-foetoprotein as well as cytogenetics. The test permitting one to establish a diagnosis is simple. The analysis is carried out on the lymphocytes in the blood.
Research : much research. In 2004, there was an international conference held at the University of Birmingham (October 13-14-15). Web site : www.atsociety.org.uk
Death : cancer and pneumonia because of respiratory infections between 10 and 20 years of age.
Cure : none. Injections of globulin will help the immune system.
DIAGNOSIS/TESTING: The diagnosis of AOA1 is based on clinical findings (including family history) and exclusion of the diagnosis of ataxia-telangiectasia. Cerebellar atrophy is visible on MRI in all affected individuals. EMG reveals axonal neuropathy in 100% of individuals with AOA1. Molecular genetic testing of APTX, the only gene associated with AOA1, is clinically available.
MANAGEMENT: Treatment of manifestations: may include physical therapy, particularly for disabilities resulting from peripheral neuropathy; a wheelchair for mobility, usually by age 15-20 years; educational support for difficulties with speaking, reading, and writing. Prevention of secondary complications: high-protein diet to prevent edema by restoring serum albumin concentration; low-cholesterol diet. Surveillance: routine follow-up with a neurologist.
GENETIC COUNSELING: AOA1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if both the disease-causing alleles in a family are known.
Source : Coutinho P, Barbot C. Ataxia with Oculomotor Apraxia Type 1. GeneReviews [Internet].
DIAGNOSIS/TESTING: The diagnosis of AOA2 is based on clinical and biochemical findings, family history, and exclusion of the diagnosis of ataxia-telangiectasia and AOA1. AOA2 is associated with mutations in the gene SETX, which encodes the protein senataxin. Molecular genetic testing is available on a clinical basis.
MANAGEMENT: Treatment of manifestations: physical therapy for disabilities resulting from peripheral neuropathy; wheelchair for mobility as needed; educational support (e.g., computer with speech recognition and special keyboard for typing) to compensate for difficulties in reading (caused by oculomotor apraxia) and in writing (caused by upper-limb ataxia). Surveillance: routine follow-up with a neurologist.
GENETIC COUNSELING: AOA2 is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. No laboratories offering prenatal testing are listed in the GeneTests Laboratory Directory; however, such testing may be available through laboratories offering custom prenatal diagnosis.
Source : Maria-Céu Moreira, Michel Koenig. Ataxia with Oculomotor Apraxia Type 2. GeneReviews [Internet].