Here is a description of a few different forms of the best known cerebellar ataxias.
Hereditary ataxias are diseases of the central nervous system.
The ataxia is generally the consequence of a cerebellar affliction which can affect the cerebellum itself or the fibres which conduct information and of which the transmission is done by the spinal chord (spinocerebellar tract). These diseases are genetic, evolutive and for the moment without cure.
Genetic disease :
-The genes of ataxias are found on a chromosome and contain all the information for the building of a protein (containing amino acids) which is situated in the interior of the mitochondria.
*Mitochondria are small corpuscles present in great numbers in the cells of the organism which have as their role to produce chemical energy coupled with the consummation of oxygen. Mitochondria contain enzymes accelerating the reactions of transferring food into energy.
Hereditary ataxias are a group of mitochondrial diseases characterized by processes of dysfunction of the mitochondria in the skeletal muscles. This brings about a progressive disease in the production of energy in the cell. When these dysfunctions repeat themselves on a large scale in the body, entire systems (nervous system, sensory system, etc.) begin to fail.
*The severity of these diseases will in fact depend on the organs which are the most affected by the dysfunction of the mitochondria.
MODE OF TRANSMISSION :
Recessive or dominant
Recessive : Both parents must be carriers in order for a child to be afflicted. The parents are in good health. According to the law of genetics, 25% of the children will be afflicted.
Dominant : Only one parent who is a carrier is necessary in order that the child be afflicted.
RECESSIVE AUTOSOMIC CEREBELLAR ATAXIAS
Here is a description of some forms of recessive ataxias (that is to say that it is obligatory that the 2 parents transmit the faulty gene in order that the child be afflicted). *Both men and women can be afflicted.
*FRIEDREICH’S ATAXIA
Definition :
Friedreich’s ataxia is a hereditary evolutive neurological disease characterized by spinocerebellar degeneration (an affliction of the tracts going from the cerebellum to the spinal chord). It starts most often in adolescence (cases in children and in adults can be found) by troubles walking and brings about a progressive handicap associated with motor troubles and cardiac affliction.
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 on the functioning of the cardiac muscle (cardiomyopathy) due to the reduced production of a protein, frataxine.
This decrease in frataxine brings about an excessive accumulation of iron on the level of 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 in order for a child to be afflicted). 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)
As the disease progresses, other symptoms are manifested 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 (difficult speech 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 beginning of the arrival of the first symptoms, the afflicted person will have to use a wheelchair in order to palliate his inability to walk.
Secondary problems :
(not in all cases)
*important to be followed up regularly.
Deformations :
(not in all cases)
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
<<frataxine>>.
-Gene X25 was discovered in 1996 on chromosome 9. The function of this gene is to make a protein : frataxine. Its role is to make oxygen circulate through the mitochondria present in each cell. However, in Friedreich’s ataxia, the frataxine is insufficient.
Little frataxine 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 :
Taking charge :
Neurological follow-up is indispensable in order to know the evolution of the disease in order to better orient oneself 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.
Cure and research :
For the moment no cure exists but the symptoms can be treated. For the duration of one year, eleven Friedreich ataxics were treated with a substance, idebenone. Studies in France proved that the mechanism which leads to the toxicity of iron plays a very important role in the development of the disease and this is why they tested this medication aiming to protect the cells from the toxic effects of iron. The results seem promising. There is hope. (See Dr. Michel Vanasse’s article on the use of idebenone in the treatment of Friedreich’s ataxia).
The researchers work on the knowledge of the function of the protein, antioxidants and other substances having a positive role on the symptoms.
*CHARLEVOIX-SAGUENAY SPASTIC ATAXIA (ARSACS)
Definition : This form of ataxia is observed solely in Saguenay-Lac St-Jean and in Charlevoix. It can be described as a degeneration of the spinal chord (affects the motor functions) as well as a progressive attack on the peripheral nerves and a sensory disturbance.
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 that of the population in general.
Characteristics :
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 :
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 :
Definition : degenerative hereditary neurological disease which affects several systems of the body. It brings about a degeneration of the cerebellum associated with dilations characteristic of certain small vessels (telangiectasia) which become visible to the naked eye.
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.
Symptoms :
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
E-mail : atcharity@aol.com
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.
DOMINANT HEREDITARY ATAXIAS
Here is a description of a few forms of dominant autosomic ataxias, that is to say that the gene of one single parent is necessary in order to transmit the disease. These dominant ataxias are classified by type-1-11-111 representing the age of appearance, the severity and the variety of the symptoms. The same thing for spinocerebellar ataxia which is categorized by around twenty types called
SCA1…SCA19.
Type 1 : one finds other neurological troubles without affecting the eye (5 genes are involved)
Type 11 : one finds other neurological signs with an affliction of the retina of the eye (relatively rare)
Type 111 : only the cerebellum is affected.
*DOMINANT AUTOSOMIC CEREBELLAR ATAXIAS
Definition : An ailment at first characterized by the association of lesions on the level of the cerebellar trunk (pons or protuberance and bulbous olive) and of the cerebellum. It can be associated with a medullar affliction approaching that of Friedreich’s. It is also a progressive destruction of the nervous tracts which connect several different structures of the encephalon (starting from the nervous system in the skull) each playing a particular role in the nervous system. This degeneration (the anatomical lesions which reach the nervous tracts) is at the origin of the cerebellar syndrome i.e. the symptoms.
The cerebellum being affected, this brings about troubles of balance and coordination.
Mode of transmission : autosomic (afflicts both sexes) and dominant ( one single parent can transmit the disease).
Age : affects the adult at a mature age (around 40 years) but precocious forms can affect children and later forms can affect seniors. The age is variable even within the same family. The disease leads to a wheelchair.
Evolution : the evolutive rhythm is often slowly progressive and extremely variable leading to a loss of autonomy.
Cause : many different genes. At least 14 of which several are known. The known mutations consist of a repeated expansion of trinucleotides of which the unstable character is at the origin of the phenomenon of anticipation since its appearance at an earlier and earlier age is observed.
Symptoms : cerebellar ataxia, problem of balance, of coordination and of elocution, sensorial losses, muscular weakness, difficulty swallowing and nystagmus.
This ataxia is a part of a group of afflictions, itself classified in 4 large groups, allowing one to better identify it according to the precise criteria of troubles associated with cerebellar ataxia.
DEFINITION :
Affliction of the cerebellum which brings about troubles of balance and of the coordination of movements.
Affliction characterized by the association of lesions on the level of the cerebellar trunk and the cerebellum and especially the white substance of the cerebellum, the cerebellar peduncle and the bulbous olives. Otherwise stated, OPCA is the progressive destruction of the nervous cells which link several different structures of the encephalon part of the central nervous system. These degenerations go right to the cerebellum. They are at the origin of the cerebellar syndrome, that is to say, the clinical signs which the afflicted person presents.
CAUSE : several genes. The expansion of trinucleotides is easily tested and confirms the diagnosis in a person belonging to a family which already has cases or even in an isolated case.
AGE : variable including in the same family. In general, around 40 years of age (always at an adult age)
EVOLUTION : slowly progressive. Variable from one individual to another. It is sometimes complicated by troubles afflicting the sphincters which are the muscles allowing the closing and the opening of orifices. Some patients present a muscular hypertrophy characterized by a contraction of the muscles.
FREQUENCY : the risk is ½ for the children of an afflicted subject.
SYMPTOMS : A cerebellar syndrome characterized thusly :
Definition : it is a hereditary spinocerebellar ataxia especially frequent in the Portuguese and the Japanese (because of immigration, it is present in Canada). This disease was discovered in 1970 but research began in 1994.
Cause : genetic. (a repeated expansion of glutamate)
Mode of transmission : dominant autosomic (afflicts both sexes and one single parent is sufficient in order to transmit the disease and afflict 50% of the children.
Races :
Portuguese, French, Chinese, Japanese, German, American (more frequent in the Portuguese and the Japanese)
Gene : the gene is still not discovered.
Appearance : the disease appears between 30 and 40 years of age and leads to a wheelchair.
Symptoms : cerebellar ataxia, ocular paralysis, difficulty swallowing, nystagmus.