Machado-Joseph disease is a neurodegenerative disease from the group of spinocerebellar ataxias. The cause of the disease is a genetic mutation that is passed on in the autosomal dominant inheritance. So far, only supportive treatment methods such as physiotherapy and ergotherapy have been available.
What is Machado-Joseph disease?
According to Deluxesurveillance, neurodegenerative diseases are characterized by pathological processes in the nervous system that lead to a loss of function of nerve cells. The group of neurodegenerative diseases consists of different subgroups.
One of these is spinocerebellar ataxia 3, a group of disorders involving central nervous system degeneration. Spinocerebellar ataxia 3 corresponds to Machado-Joseph disease ( MJD ). As the disease progresses, Purkinje cells progressively die. These are the largest nerve cells in the cerebellum and are located in the stratum ganglionare of the cerebellar cortex.
Purkinje cells are equipped with metabotropic glutamate receptors that serve to modulate and integrate motor efferents and thus enable the learning of movement sequences. The prevalence of spinocerebellar ataxia is one to nine cases in 100,000 people. Machado-Joseph disease is the most common form in Germany.
Machado-Joseph disease is an inherited condition. As with all other hereditary disorders, the primary cause of spinocerebellar ataxia 3 is genetic. Machado-Joseph disease is inherited in an autosomal dominant manner. Familial clusters have therefore been observed in the cases documented to date.
A sporadic occurrence without familial accumulation is rather rare. A genetic mutation is inherited in Machado-Joseph disease. This change in genetic material affects that on chromosome 14 in gene locus q24.3-32.1. The gene located there no longer does justice to its physiologically intended coding and lengthens the polyglutamine region as a result of the mutation.
More than a dozen different genes have been identified as mutation sites for spinocerebellar ataxias. In the course of MJD, unlike other forms of spinocerebellar ataxia, the mutation causes progressive degeneration of the defective Purkinje cells, which predominantly leads to movement disorders.
Symptoms, Ailments & Signs
Patients with Machado-Joseph disease suffer from disorders of the motor coordination center. This movement center is located in the cerebellum and is connected to the Purkinje cells, which in a healthy organism control the integration of motor movement signals via their metabotropic glutamate receptors.
Since the Purkinje cells of patients with Machado-Joseph disease progressively degenerate, the motor functions of those affected are particularly impaired. In middle age, unspecific movement disorders increasingly occur. Those affected perform apparently nonsensical movement patterns, since their control center no longer integrates the motor efferents in a meaningful way, making movement planning more difficult.
MJD initially manifests itself mostly in eye movements without a logical pattern. The fixation seems to be complicated by the movements. As the disease progresses, the sense of direction is impaired.
Severe disturbances of perception are added to the symptoms. Although the symptoms in individual cases depend on the severity of the course, there is usually at least a moderate disability from a certain point in time.
Diagnosis & course of disease
The diagnosis of Machado-Joseph disease is made on the basis of the clinical symptoms, with the characteristic eye movements being the main diagnostic factor in the early stages. The family history is a crucial point in the diagnosis. At first glance, it is difficult to distinguish the disease from other spinocerebellar ataxias in terms of differential diagnosis.
Brain imaging shows typical changes within the cerebellum. A molecular genetic analysis, which provides evidence of the associated mutation, can confirm the diagnosis and serve as a basis for differential diagnosis. The prognosis for patients with Machado-Joseph disease depends on the symptoms and course in the individual case.
The life expectancy of those affected is usually not affected. However, for particularly severe courses, multiple disabilities are to be expected, which are associated with more or less high levels of care. Milder cases with moderate impairment in everyday life have also been documented.
Those affected by Machado-Joseph disease primarily suffer from various coordination or concentration disorders. The everyday life of those affected is significantly restricted by this disease, so that in some cases they are dependent on the help of other people. Furthermore, the general condition of the patient deteriorates over the course of the disease, so that movement disorders continue to occur.
The motor skills of the patients are also reduced and there are problems with movement planning. Not infrequently, orientation also suffers from Machado-Joseph disease, so that those affected are often confused and do not know where they are. However, the exact symptoms and complications depend very much on the severity and general condition of the patient. As a rule, Machado-Joseph disease leads to intellectual disability in the patient.
There is no causal treatment for Machado-Joseph disease. For this reason, only the symptoms and complaints can be limited, although the course of the disease will not be completely positive. However, the life expectancy of those affected is not reduced by the disease. The patients are then dependent on various therapies that can make their everyday life easier.
When should you go to the doctor?
If a newborn child shows mobility problems, a medical examination is required. In many cases, pediatricians or nursing staff can detect the first irregularities in movement immediately after the birth. You initiate the necessary steps for medical care independently in a routine process. If the first abnormalities occur during the growth process of the child, a pediatrician should be consulted. If movements are unusual or if the parents interpret them as nonsensical, the observations should be presented to a doctor.
If the eye movements are perceived as abnormal, there is cause for concern. As soon as they make no sense and last for several days or weeks, a medical examination is advisable. If the child has visible difficulties in planning movement or if disorientation is recognizable, medical help is required.
If children show problems in fixing objects and at the same time with their own movement sequences in reaching the goal, there is a disease. In order to determine the cause of the symptoms, a doctor’s visit is necessary. In the case of a disturbance of perception, learning problems or a developmental delay, a visit to a doctor is necessary. If there are major differences in memory or locomotion in direct comparison to children of the same age, a doctor should be consulted.
Treatment & Therapy
Machado-Joseph disease is one of the incurable diseases. A causal therapy is therefore not available for patients with the movement disorders. Causal therapies resolve the cause of a disease in order to make all symptoms disappear.
Since the cause of spinocerebellar ataxia lies in the genes, only gene therapy approaches could offer a causal treatment and the associated cure. Gene therapy is currently a focus of medical research. However, the approaches have not yet reached the clinical phase. Therefore, patients with Machado-Joseph disease have so far only been treated supportively.
Symptomatic treatment approaches are very limited, which is not least due to the rarity of the disease in the US and Central Europe. The supportive treatment measures include above all physiotherapy and ergotherapy. In occupational therapy in particular, those affected learn to deal with the disease in everyday life.
The use of different aids and other compensation strategies makes everyday life easier for them and increases their quality of life. In addition, those affected are usually offered psychotherapy. Together with an experienced therapist, they deal with their illness and process the diagnosis.
Psychotherapeutic support can also be a useful step in processing for family members. Genetic counseling is just as important for affected families. Drug treatment approaches to delay the course of the disease do not yet exist. However, regular physical therapy has been speculated to delay progression.
Outlook & Forecast
The outlook for people with Machado-Joseph disease is fair. The course of Machado-Joseph disease varies from person to person. This disease is caused genetically. So far, the symptoms of Machado-Joseph disease can only be alleviated in a supportive manner. In addition, the hereditary disease progresses over the years. By midlife at the latest, Machado-Joseph disease causes significant disabilities and increasing mobility restrictions. With aging, the prospects of a symptom-free life therefore increasingly deteriorate.
However, the prospects for the course of the disease depend on the symptoms present. Most of the time, the life expectancy of those affected is not affected by Machado-Joseph disease. The problem, however, is that there are those affected with particularly severe courses. These patients have multiple disabilities. These result in a need for care, which can exist in different degrees. The reason for this is a more or less severe disturbance of movement coordination.
Despite an overall mediocre prognosis, milder cases of Machado-Joseph disease have also been documented in those affected, in which motor disorders led to moderate to moderate impairments in everyday life. The sense of direction also becomes increasingly disturbed as Machado-Joseph disease progresses. As the condition of those affected deteriorates, the degree of disability or need for care often increases over the course of the disease. As a minimum, a moderate degree of disability can be assumed for older affected persons.
Like all other hereditary diseases, Machado-Joseph disease can only be prevented with genetic counseling during the family planning phase. Couples who are at higher risk may choose not to have children of their own and opt for adoption.
Since the treatment of Machado-Joseph disease is complex and lengthy, there is no follow-up care in the true sense. Rather, it appears as an accompanying measure to achieve safe handling of the disease. Those affected should try to build a positive attitude despite the difficult circumstances. Relaxation exercises and meditation can help calm and focus the mind.
Those affected are usually permanently dependent on the help of relatives, since everyday life is significantly restricted by the disease. The doctors treating you try to limit the symptoms so that it is easier for those affected to lead a normal life. Machado-Joseph disease cannot be cured. Patients have to undergo various therapies over the long term in order to be able to lead a normal life. In order to cope better with the stress, it can help to seek psychological support.
You can do that yourself
Machado-Joseph disease is a genetic disease that cannot be cured. It is progressive and leads to ataxia in the affected person, the movement sequences are impaired.
This impairment can be counteracted at least partially with physiotherapy. It has already been shown that the progression of the disease can be slowed down by physiotherapy. In general, it is important that the patient does not give up and continues to move as well as possible. Sometimes the brain is also affected by the disease. If speaking is impaired, logopedic measures can lead to an improvement.
Unfortunately, the progression of Machado-Joseph disease is not possible with the measures available today. Physical and mental disabilities often result from the progression of the disease. This can lead to psychological distress for the person concerned. The social environment consisting of partner, family and friends can provide psychological support for the person concerned and help him to cope with everyday life. In addition, the care of a psychotherapist is helpful, as they can professionally care for the person affected during the ongoing illness. If the affected person has a family, it is important that the family undergoes genetic testing and counseling as the condition can be genetically inherited.