Tarui disease

Of the Tarui disease is a glycogen storage disease caused by a mutation in the PFKM gene on chromosome 12. The patients suffer from muscle cramps and are virtually exercise intolerant. Symptomatic treatment consists mainly of dietary measures and avoidance of exercise.

What is Tarui Disease?

Tarui's disease is characterized by various clinical symptoms. The most important characteristics include muscle spasms with myoglobinuria, which patients describe as stress-dependent.
© peterschreiber.media - stock.adobe.com

Many different groups of diseases fall into 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 then no longer or only partially broken down or converted into glucose. The cause of all glycogen storage diseases are enzymatic defects in the context of glycogen breakdown, gluconeogenesis or glycolysis.

A disease from the group of glycogen storage diseases is Glycogenosis type 7, which are also called Tarui disease is known. It was first described in the 20th century. The Japanese professor of internal medicine Seiichiro Tarui, who bequeathed his name to the disease, is considered to be the first to describe it. The disease manifests itself in early childhood and is classified under hereditary metabolic diseases.

causes

The cause of Tarui disease is a genetic defect. The disease does not seem to occur sporadically but with a familial accumulation. Therefore, modern medicine assumes a hereditary basis. An autosomal recessive inheritance is assumed to be the underlying inheritance of Tarui disease. Those affected show mutations in the PFKM gene on chromosome 12. So far, 15 different mutations have been linked to the symptoms of the disease.

The affected gene locus is on 12q13.3. The PFKM gene codes in the DNA for the enzyme phosphofructokinase, which performs crucial tasks in the metabolism of muscles. 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 influence on gluconeogenesis and glycolysis. In particular, the synthesis failure of fructose-1,6-bisphosphate inhibits glycolysis. It has not yet been conclusively clarified whether, in addition to the genetic factors, external factors also favor 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 stress-dependent. In addition, in most cases there is haemolytic anemia. Anemia usually leads to persistent exhaustion and fatigue.

These symptoms go back to the failure of the fructose-1,6-bisphosphate synthesis and give the patient a noticeable exercise intolerance. In some cases, those affected have to vomit under stress or at least feel extreme nausea. Some patients show, in addition to anemia, an increase in reticulocytes and hyperbilirubinemia. Exercise-dependent hyperuricemia was also observed in the cases documented so far.

The increased uric acid level in the blood can in the long run cause symptoms of gout and favor soft tissue or bone entophi. In addition, kidney disease can develop in the later course. Most of the time, the stress-related symptoms of Tarui disease manifest in particular in kindergarten age.

Diagnosis & course of disease

The diagnosis of Tarui disease begins with the anamnesis. If the doctor suspects Tarui disease due to the characteristic stress pain and, for example, the description of gout complaints, 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 can also provide evidence of the pathological increase after exposure. Molecular genetic tests confirm the diagnosis by showing the characteristic mutations in the PFKM gene on chromosome 12.

Complications

In most cases, those affected by Tarui 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 during exertion, so that the everyday life of the patient is significantly restricted by Tarui's disease. The patient becomes less able to exercise and becomes tired.

Furthermore, the anemia leads to permanent exhaustion, which cannot be compensated for with the help of sleep. They also suffer from nausea and vomiting, which reduces their quality of life. As the disease progresses, gout symptoms develop without treatment. The kidneys can also be damaged by this disease, so that in the worst case, kidney failure can occur, which is a life-threatening condition for those affected.

This then has to rely on dialysis or a kidney transplant. This disease is usually treated with a strict diet and, if necessary, bone marrow donation. There are no complications. However, not all complaints can be completely limited. 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 complaints and impairments of the muscles should consult a doctor. A restriction of mobility, an impossibility of locomotion and cramps in 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 doctor should clarify a low level of physical resilience and performance. If everyday life cannot be mastered independently due to the impairments, there is a need for action. Persistent exhaustion, pale skin and a strong sensation of cold in the body indicate irregularities that should be examined and treated.

Usually there is anemia, which affects the entire functioning of the organism and causes slow body movements and rapid exhaustion. Irregularities in digestion, a change in toilet use and a diffuse feeling of illness should be presented to a doctor. If you experience pain in the kidney area, abnormal urine volume, color, or smell of the urine, you should consult a doctor. If the person concerned suffers nausea or vomiting while coping with everyday tasks, a visit to a doctor is advisable. There is a special need for action if even slight physical movements lead to malaise and vomiting. Consultation with a doctor is also advisable in the event of disorders of concentration and attention as well as behavioral problems.

Therapy & Treatment

A causal therapy is currently not available for patients with Tarui disease. For this reason, the disease has so far been considered incurable. However, since gene therapy measures are a current research subject in medicine that has not yet reached the clinical phase, causal therapies for various genetic diseases may be cured by causal therapies in the near future.

So far, Tarui disease patients have been treated purely symptomatically. The most important steps in therapy include taking physical care and avoiding heavy physical stress. Dietary measures have also been recommended as therapeutic steps for patients with Tarui 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 with a high-carbohydrate diet. For this reason, a low-carbohydrate diet can, conversely, increase the patient's performance. The administration of drugs to eradicate hemolytic anemia has not proven effective in the past for patients with Tarui disease.

The same goes for bone marrow donations. Since the cause of the anemia cannot be eliminated in the context of Tarui's disease, it is difficult to correct. The parents of affected children usually receive advice on how to deal with their child as part of the therapy. You can also take advantage of genetic counseling if you want to have children and want to find out about the risk of recurrence and the general relationships between inheritance.

You can find your medication here

➔ Medicines for pain

Outlook & forecast

Tarui disease is an extremely rare disease. The prognosis for suffering is relatively poor. Due to the small number of cases described, the condition is usually recognized late and not treated comprehensively. This leads to a reduced performance and a reduced sense of wellbeing. Sick people must not exert themselves physically to avoid an increase in muscle pain and other symptoms. This severely limits the patient's professional opportunities. In connection with the reduced exercise tolerance, mental complaints can develop that need to be treated.

If depression or anxiety disorders develop as a result of Tarui disease, the prospect of recovery is poor. Due to the progressive course, the psychological problems often increase and the sick have to take strong medication. Therapy can only relieve symptoms to a limited extent. However, life expectancy is not necessarily affected by Tarui's disease. Symptomatic therapy is effective and in many cases enables sufferers to live a long life. The specialist in charge makes the exact prognosis based on the patient's individual symptoms.

prevention

Since Tarui's disease corresponds to a genetic disease caused by mutation, there are no preventive measures to date. At most, genetic counseling in family planning and, if necessary, a decision against having one's own children, if there is a family disposition for Tarui disease, can be equivalent to prevention.

Aftercare

As a rule, patients with Tarui’s disease usually have only a few and only limited follow-up measures available, as this disease is a genetic disease that cannot be completely cured. Therefore, the person concerned should first and foremost consult a doctor very early to prevent further complications from occurring.

If you want to have children, a genetic examination and counseling can also be carried out so that the recurrence of Tarui disease in the descendants can be prevented. As a rule, those affected with this disease are dependent on a special diet, whereby the doctor can create a nutrition plan. This should be adhered to as well 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 strain if possible. Regular checks by a doctor are also very important in order to identify and treat damage to the body at an early stage. Not infrequently, contact with other people affected by the disease is also very useful, as this can lead to an exchange of information, which makes everyday life easier for those affected.

You can do that yourself

Tarui disease cannot yet be treated causally. The self-help measures focus on supporting symptomatic therapy and thus promoting the healing process.

Dietary measures can also be used in the treatment of Tarui disease. Avoiding carbohydrates can lead to an increase in free fatty acids and ketone bodies.This increases the performance of those affected. When taking medication, a change in diet has a major impact on the mental and physical health of the patient.

Adequate rest is a prerequisite for a positive healing process. Symptoms such as anemia in particular contribute to increasing tiredness, which significantly restricts those affected in their everyday lives. It is important here to take appropriate measures to increase physical activity. Ideally, active phases are alternated with phases of rest and relaxation.

The doctor in charge can best answer which measures are to be taken in detail. They can also refer the affected person to a specialist clinic for genetic diseases. Comprehensive advice on the risks for the child is particularly important for parents-to-be who suffer from Tarui disease.