Tarui disease is a glycogen storage disease caused by a mutation in the PFKM gene on chromosome 12. Patients suffer from muscle spasms and are virtually exercise intolerant. Symptomatic treatment consists primarily of dietary measures and avoidance of stress.
What is Tarui Disease?
Many different disease groups fall under the category of metabolic diseases. One of them is the group of glycogen storage diseases. In these diseases, the glycogen is stored in the body tissues and is then no longer or only partially broken down or converted to glucose. All glycogen storage diseases are caused by enzymatic defects in the context of glycogen breakdown, gluconeogenesis or glycolysis. See growtheology for Comprehensive Guide to Keratoconjunctivitis Sicca.
A disease from the group of glycogen storage diseases is glycogenosis type 7, which is also known as Tarui disease. It was first described in the 20th century. The Japanese professor of internal medicine Seiichiro Tarui, who gave his name to the disease, is considered to be the first to describe it. The disease manifests itself in early childhood and is classified as a hereditary metabolic disease.
The cause of Tarui’s disease is a genetic defect. The disease does not appear to be sporadic, but tends to run in families. Therefore, modern medicine assumes a hereditary basis. An autosomal recessive inheritance is assumed to be the underlying inheritance of Tarui’s disease. Those affected show mutations in the PFKM gene on chromosome 12. So far, 15 different mutations have been associated with the symptoms of the disease.
The affected gene locus is at 12q13.3. The PFKM gene codes in the DNA for the enzyme phosphofructokinase, which performs crucial tasks in muscle metabolism. Mutations in the PKFM gene result in a defect in the enzyme that causes the symptoms of Tarui disease.
Because of the enzymatic defect, metabolic intermediates accumulate, which in turn have an inhibitory effect on gluconeogenesis and glycolysis. In particular, failure of the synthesis of fructose-1,6-bisphosphate inhibits glycolysis. It has not yet been conclusively clarified whether, in addition to genetic factors, external factors also promote the disease.
Symptoms, Ailments & Signs
Tarui’s disease is characterized by various clinical symptoms. The most important characteristics include muscle spasms with myoglobinuria, which patients describe as being exercise-related. In addition, in most cases there is haemolytic anemia. Anemia usually leads to persistent exhaustion and fatigue.
These symptoms are due to the failure of fructose-1,6-bisphosphate synthesis and give the patient a conspicuous exercise intolerance. In some cases, those affected have to vomit under stress or at least feel extreme nausea. Some patients show an increase in reticulocytes and hyperbilirubinemia in addition to anemia. Stress-related hyperuricemia has also been observed in the cases documented to date.
The increased uric acid level in the blood can cause gout symptoms in the long term and promote soft tissue or bone tophi. In addition, kidney disease can develop later. The stress-related symptoms of Morbus Tarui usually manifest themselves in kindergarten age at the latest.
Diagnosis & course of disease
The diagnosis of Tarui’s disease begins with the anamnesis. If the doctor has a first suspicion of Tarui’s disease due to the characteristic stress pain and, for example, the description of gout symptoms, a stress test can confirm the suspected diagnosis.
To confirm the diagnosis, the doctor orders muscle biopsies to demonstrate the reduced enzyme activity in the muscle tissue and also has the erythrocytes examined. A survey of the uric acid level in the blood after exertion can also provide evidence of the pathological increase. Molecular genetic studies confirm the diagnosis by showing the characteristic mutations in the PFKM gene on chromosome 12.
In most cases, sufferers of Tarui’s disease suffer from severe muscle cramps. These lead to severe pain and, in the worst case, can even lead to death. In most cases, these cramps also occur under stress, so that the patient’s everyday life is significantly restricted by Tarui’s disease. The patient has reduced resilience and fatigue.
Furthermore, anemia leads to permanent exhaustion, which cannot be compensated for with the help of sleep. Those affected also suffer from nausea and vomiting, which reduces the quality of life. As the disease progresses, gout symptoms develop if left untreated. The kidneys can also be damaged by this disease, so that in the worst case it can lead to kidney failure, which is a life-threatening condition for those affected.
The patient is then dependent on dialysis or a kidney transplant. This disease is usually treated with a strict diet and, if necessary, a bone marrow donation. There are no complications. However, not all complaints can be completely curbed. Whether the disease leads to a reduction in life expectancy depends heavily on the severity of the disease and the type of treatment.
When should you go to the doctor?
People who suffer from discomfort and impairment of the muscles should consult a doctor. Restricted mobility, the impossibility of moving and spasms of the muscular system must be examined and treated. If the person concerned suffers from tiredness, exhaustion or an inner weakness, he needs medical help. A low physical resilience and performance should be clarified by a doctor. If everyday life cannot be managed independently due to impairments, there is a need for action. Persistent exhaustion, a pale complexion and a strong feeling of cold in the body indicate irregularities that should be examined and treated.
In most cases, anemia is present, which affects the entire functional activity of the organism and causes slow body movements and rapid exhaustion. Irregularities in digestion, a change in toileting and a diffuse feeling of illness should be presented to a doctor. If there is pain in the kidney area, an abnormality in the amount of urine, color or smell of the urine, a doctor should be consulted. If the person concerned experiences nausea or vomiting while coping with everyday tasks, a doctor’s visit is advisable. There is a special need for action if even slight physical movements lead to discomfort and vomiting. In the case of disturbances in concentration and attention as well as behavioral problems, it is also advisable to consult a doctor.
Treatment & Therapy
A causal therapy is not yet available for patients with Tarui’s disease. For this reason, the disease has so far been considered incurable. However, since gene therapy measures are a current research topic in medicine, which has not yet reached the clinical phase, causal therapies for various gene diseases can possibly be cured by causal therapies in the near future.
So far, patients with Tarui’s disease have been treated purely symptomatically. The most important steps in therapy include resting and avoiding heavy physical exertion. Dietary measures have also been recommended as therapeutic steps for patients with Tarui’s disease in the past.
For example, the intake of carbohydrates leads to a reduction in free fatty acids and ketone bodies. The performance of those affected decreases even more through carbohydrate-rich food. For this reason, a low-carbohydrate diet can, in turn, increase the patient’s performance. In the past, the administration of medication to eliminate hemolytic anemia has not proved successful for patients with Tarui’s disease.
The same applies to bone marrow donations. Since the cause of anemia in Tarui disease cannot be eliminated, it is difficult to correct. As part of the therapy, the parents of affected children usually receive advice on how to deal with their child. You can also take advantage of genetic counseling if you wish to have more children and want to find out more about the risk of recurrence and the general context of heredity.
Outlook & Forecast
Tarui disease is an extremely rare disease. The prognosis of the condition is relatively poor. Due to the small number of cases described, the condition is usually recognized late and not treated comprehensively. This is accompanied by reduced performance and reduced well-being. Patients should not exert themselves strenuously to avoid increasing muscle pain and other symptoms. This severely limits the patient’s career options. In connection with the reduced stress tolerance, psychological problems can develop that need to be treated.
Once depression or anxiety disorders have developed as a result of Tarui’s disease, the prospects for recovery are poor. Due to the progressive course, the psychological problems often increase and the sufferers have to take strong medication. Therapy can only alleviate symptoms to a limited extent. However, life expectancy is not necessarily affected by Tarui disease. Symptomatic therapy is effective and in many cases allows sufferers to live a long life. The specialist doctor responsible makes the exact prognosis with regard to the individual symptom picture of the patient.
Since Tarui’s disease corresponds to a genetic disease caused by mutation, there are currently no preventive measures. At most, genetic counseling in family planning and, if necessary, the decision not to have children if there is a family disposition for Tarui’s disease can be tantamount to prevention.
As a rule, the patient with Tarui’s disease has only a few and only limited follow-up measures available, since this disease is a genetic disease that cannot be completely cured. Therefore, the affected person should primarily consult a doctor very early on to prevent the occurrence of further complications.
If you wish to have children, a genetic examination and counseling can also be carried out so that the recurrence of Tarui’s disease in the descendants can be prevented. As a rule, those affected by this disease are dependent on a special diet, whereby a nutrition plan can be drawn up by the doctor. This should be adhered to as closely as possible, whereby a healthy lifestyle generally has a positive effect on the further course of the disease.
Those affected should avoid unnecessary exertion or physical stress if possible. Regular check-ups by a doctor are also very important in order to identify and treat damage to the body at an early stage. It is not uncommon for contact with other people affected by the disease to be very useful, since this can lead to an exchange of information, which makes everyday life easier for those affected.
You can do that yourself
Morbus Tarui cannot be treated causally so far. The self-help measures focus on supporting the symptomatic therapy and thus promoting the healing process.
Dietary measures can also be used in the treatment of Tarui’s disease. For example, avoiding carbohydrates can lead to an increase in free fatty acids and ketone bodies. This increases the performance of those affected. Along with taking medication, a change in diet has a significant impact on the mental and physical health of patients.
However, a prerequisite for a positive healing process is sufficient protection. Above all, symptoms such as anemia contribute to increasing tiredness, which significantly restricts those affected in their everyday lives. It is important to take appropriate measures to increase physical activity. Ideally, active phases are alternated with phases of rest and relaxation.
The responsible doctor can best answer the detailed measures to be taken. This can also refer the person concerned to a specialist clinic for genetic diseases. Comprehensive advice about the risks for the child is particularly important for expectant parents who suffer from Morbus Tarui.