Tarui disease is a glycogen storage disorder caused by a mutation in the PFKM gene on chromosome 12. Patients suffer from muscle spasms and are virtually exercise intolerant. Symptomatic treatment consists mainly of dietary measures and exercise avoidance.
What is Tarui’s disease?
Many different disease groups fall into the category of metabolic diseases. One of them is the group of glycogen storage diseases. These diseases involve glycogen being stored in body tissues and then not being broken down or turned into glucose, or only partially. All glycogen storage diseases are caused by enzymatic defects in glycogen degradation, gluconeogenesis or glycolysis. One disease from the group of glycogen storage diseases is glycogenosis type 7, also known as Tarui’s disease. It was first described in the 20th century. The Japanese professor of internal medicine Seiichiro Tarui is considered the first describer, and he bequeathed his name to the disease. The disease manifests in early childhood and is included among the hereditary metabolic diseases.
Causes
The cause of Tarui’s disease is a genetic defect. The disease does not appear to occur sporadically, but with familial clustering. Therefore, modern medicine assumes a hereditary basis. The underlying mode of inheritance of Tarui disease is thought to be autosomal recessive. Affected individuals show mutations of the PFKM gene on chromosome 12. 15 different mutations have been associated with the symptoms of the disease to date. The affected gene locus is located on 12q13.3. The PFKM gene codes in DNA for the enzyme phosphofructokinase, which plays critical roles in muscle metabolism. Mutations in the PKFM gene result in a defect of the enzyme, which causes the symptoms of Tarui disease. Due to the enzymatic defect, metabolic intermediates accumulate, which in turn show an inhibitory effect on gluconeogenesis and glycolysis. In particular, the synthesis of fructose-1,6-bisphosphate inhibits glycolysis. Whether external factors in addition to genetic factors promote the disease has not yet been conclusively determined.
Symptoms, complaints, and signs
Tarui disease is characterized by various, clinical symptoms. The most important characteristics include muscle spasms with myoglobinuria, which patients describe as load-dependent. In addition, hemolytic anemia is present in most cases. The anemia usually results in persistent fatigue and exhaustion. These symptoms are due to failure of fructose-1,6-bisphosphate synthesis and give patients a striking exercise intolerance. In some cases, affected individuals vomit under stress or at least experience extreme nausea. In addition to anemia, some patients show an increase in reticulocytes and hyperbilirubinemia. Exercise-induced hyperuricemia has also been observed in cases documented to date. The elevated blood uric acid level may cause gouty symptoms in the long term and promote soft tissue or bone entophi. In addition, kidney disease may develop later in the course of the disease. In most cases, specifically the strain-related symptoms of Tarui’s disease manifest at the latest in kindergarten age.
Diagnosis and course of the disease
Diagnosis of Tarui disease begins with the patient’s medical history. If the physician has an initial suspicion of Tarui disease based on the characteristic exertional pain and, for example, the description of gout symptoms, an exertional test can confirm the suspected diagnosis. To confirm the diagnosis, the physician orders muscle biopsies for evidence of reduced enzyme activity in 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 elevation after stress. Molecular genetic testing confirms the diagnosis by showing the characteristic mutations in the PFKM gene on chromosome 12.
Complications
As a result of Tarui disease, affected individuals suffer from severe muscle spasms in most cases. These lead to severe pain and, in the worst cases, can lead to death. In most cases, these cramps also occur during exertion, so that the daily life of patients is significantly limited by Tarui disease.The patient suffers from reduced resilience and fatigue. Furthermore, anemia leads to permanent exhaustion, which cannot be compensated by sleep. Patients also suffer from nausea and vomiting, which reduces the 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, renal insufficiency can occur, which is a life-threatening condition for the affected person. The patient is then dependent on dialysis or a kidney transplant. Treatment of this disease is usually by means of a strict diet and, if necessary, a bone marrow donation. Complications do not occur. However, not all symptoms can be completely limited. Whether there is a reduction in life expectancy due to the disease depends largely on the severity of the disease and the type of treatment.
When should you see a doctor?
People who suffer from discomfort and impairment of the musculature should see a doctor. A reduction in mobility, an inability to move, and spasms of the muscular system should be examined and treated. If the affected person suffers from fatigue, exhaustion or an internal weakness, he or she needs medical help. Low physical resilience and performance should be clarified by a physician. If everyday life cannot be managed independently due to the impairments, action is required. Persistent exhaustion, a pale complexion and a strong sensation of cold in the body indicate irregularities that should be investigated and treated. In most cases, anemia is present, which has an effect on the overall functioning of the organism, causing slow body movements and rapid exhaustion. Irregularities in digestion, a change in going to the toilet, and a diffuse feeling of illness should be presented to a doctor. If there is pain in the area of the kidneys, an abnormality in the amount, color or odor of urine, a physician should be consulted. If the affected person experiences nausea or vomiting while performing everyday tasks, a visit to the doctor is advisable. Special action is required if even slight physical movements lead to malaise and vomiting. Consultation with a physician is also advisable in the event of disturbances in concentration and attention as well as behavioral problems.
Treatment and therapy
A causal therapy is not yet available for patients with Tarui’s disease. For this reason, the disease is considered incurable to date. However, because gene therapy is a current area of medical research that just has not yet reached the clinical stage, causal therapies for various gene diseases may eventually be cured by causal therapies in the near future. To date, patients of Tarui’s disease have been treated purely symptomatically. Among the most important steps in therapy are physical rest and avoidance of strenuous physical exertion. Dietary measures have also been recommended as therapeutic steps for Tarui disease patients in the past. For example, carbohydrate intake leads to a decrease in free fatty acids and ketone bodies. Thus, the performance of the affected person decreases even more with a high-carbohydrate diet. For this reason, a low-carbohydrate diet can, in contrast, increase the performance of patients. The administration of medications to eliminate hemolytic anemia has not proven effective for patients with Tarui’s disease in the past. The same is true for bone marrow donations. Since the cause of anemia cannot be eliminated in Tarui’s disease, it is difficult to correct. The parents of affected children usually receive counseling on how to deal with their child as part of the therapy. They may additionally seek genetic counseling if there is a further desire to have children and they wish to inquire about the risk of recurrence and the general relationships of inheritance.
Prospect and prognosis
Tarui disease is an extremely rare condition. The prognosis of the condition is relatively poor. Because of the small number of cases described, the condition is usually recognized late and not treated comprehensively.This is accompanied by reduced performance and a reduced sense of well-being. Sufferers must not exert themselves physically to avoid an increase in muscle pain and other symptoms. As a result, patients’ occupational options are severely limited. In conjunction with the reduced stress tolerance, psychological complaints may develop that need to be treated. Once depression or anxiety disorders have developed as a result of Tarui’s disease, the outlook for recovery is poor. Due to the progressive course, psychological problems often increase and sufferers have to take strong medication. Therapy can alleviate symptoms only to a limited extent. However, life expectancy is not necessarily affected by Tarui’s disease. Symptomatic therapy is effective and in many cases allows sufferers to live a long life. The exact prognosis is made by the specialist in charge with regard to the patient’s individual symptom picture.
Prevention
Since Tarui disease corresponds to a genetic disease by mutation, no preventive measures exist to date. At most, genetic counseling in family planning and, if necessary, the decision not to have one’s own children, if there is a familial predisposition to Tarui disease, can be equivalent to prevention.
Follow-up
As a rule, only a few and also only limited measures of aftercare are usually available to the patient with Tarui’s disease, since this disease is a genetic disease, which in the process also cannot be completely cured again. Therefore, the affected person should first and foremost consult a doctor at a very early stage in order to prevent the occurrence of further complications. If the patient wishes to have children, genetic testing and counseling can also be performed to prevent the recurrence of Tarui’s disease in the descendants. As a rule, those affected by this disease are dependent on a special diet, whereby a diet plan can be drawn up by the doctor. This should be adhered to as well as possible, with a healthy lifestyle generally having a positive effect on the further course of the disease. Patients should avoid unnecessary exertion or physical strain as much as possible during the course of the disease. Regular check-ups by a doctor are also very important in order to detect and treat damage to the body at an early stage. Not infrequently, contact with other sufferers of the disease is also very useful, as this can lead to an exchange of information, which facilitates the everyday life of the affected person.
What you can do yourself
Tarui’s disease cannot be treated causally so far. 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. For example, avoiding carbohydrates can lead to an increase in free fatty acids and ketone bodies. As a result, the performance of those affected increases. Accompanying the intake of medication, a change in diet has a significant influence on the mental and physical health of patients. However, sufficient rest is also a prerequisite for a positive healing process. Symptoms such as anemia, in particular, contribute to increasing fatigue, which considerably restricts the affected person in his or her everyday life. Here it is important to take appropriate measures to increase physical activity. Ideally, active phases are alternated with phases of rest and relaxation. The physician in charge can best answer the question of which measures to take in detail. He or she can also refer the patient to a clinic specializing in genetic diseases. Especially for expectant parents suffering from Tarui’s disease, comprehensive advice about the risks for the child is important.
