Glucose-6-phosphate dehydrogenase deficiency is a hereditary deficiency of the enzyme glucose-6-phosphate dehydrogenase, which plays an important role in sugar metabolism. The symptoms of the deficiency are highly variable, and in severe cases, destruction of red blood cells in the form of hemolysis may occur. The condition is easily controlled by avoiding certain foods and medications.
What is glucose-6-phosphate dehydrogenase deficiency?
Glucose-6-phosphate dehydrogenase deficiency characterizes a deficiency or defective mode of action of the enzyme glucose-6-phosphate dehydrogenase. The consequences of this deficiency vary. Thus, symptoms vary from asymptomatic to hemolytic crises. Since the disease is inherited via the X chromosome, women are usually less affected than men. Mainly in malaria areas this enzyme deficiency is widespread. Triggers of hemolytic crises are often beans (Fava beans) and certain drugs such as primaquine, nitrofurantoin or sulfanilamide. Because it is triggered by fava beans, glucose-6-phosphate dehydrogenase deficiency is also known as favism when symptoms are present. Approximately 400 million people worldwide are affected by this enzyme defect. Most people, mainly women, do not develop any symptoms at all. As a rule, quality of life and life expectancy are not limited in glucose-6-phosphate dehydrogenase deficiency. Only hemolysis-triggering foods and drugs should be avoided in severe forms.
Causes
The cause of glucose-6-phosphate dehydrogenase deficiency is a mutation of the G6PD gene on the X chromosome. This gene is responsible for encoding the enzyme glucose-6-phosphate dehydrogenase. The expression of the symptoms depends on the specific mutation and on the sex of the person. To date, approximately 150 mutations of this gene are known. The function of the enzyme is not equally restricted in every mutation. Girls and women have two G6PD alleles. In most cases, the defective gene is passed on heterozygously. This means that there are still enough healthy G6PD genes from the other parent. In males, the second gene is missing, so that the glucose-6-phosphate dehydrogenase deficiency is more pronounced. Furthermore, the mutation present determines the residual activity of the enzyme. The enzyme glucose-6-phosphate dehydrogenase plays a crucial role in carbohydrate metabolism. It is responsible for the conversion of oxidized NADP+ into reduced NADPH. NADH in turn represents a cofactor of the enzyme glutathione reductase. Glutathione reductase reduces the dimeric oxidized glutathione to two monomers of reduced glutathione. In its reduced form, glutathione is a potent antioxidant and scavenges free radicals. In the case of a deficiency of reduced glutathione, the capacity for the destruction of free radicals is often insufficient. This is especially true when many radical intermediates are formed by intake of external substances. Fava beans, peas or currants, for example, contain certain alkaloids that give rise to radical degradation products. A similar situation applies to certain drugs. If too little reduced glutathione is present, the free radicals are only inadequately broken down. Their concentration can increase to the point where they destroy erythrocytes, triggering hemolysis. The lack of reduced glutathione is in turn the result of a lack of NADH. Because the formation of NADH is catalyzed by glucose-6-phosphate dehydrogenase, insufficient activity of this enzyme also results in insufficient new formation of NADH from NAD+.
Symptoms, complaints, and signs
Glucose-6-phosphate dehydrogenase deficiency manifests itself in different ways. Three different forms of expression are distinguished in broad outline. Thus, a symptom-free form of enzyme deficiency exists. In these cases, sufficient active enzymes are still present to compensate for the deficiency. A second form is acute hemolytic anemia, which is triggered by fava beans, sulfonamides, vitamin K, naphthalene or acetylsalicylic acid. The rarest is chronic hemolytic anemia, in which red blood cells die permanently. In this case, the formation of new blood cells cannot fully compensate for their degradation. When the symptoms become pronounced, the symptoms include chills, fever, weakness, shock, back pain or abdominal pain.The urine turns black. Furthermore, jaundice occurs. Newborns with glucose-6-phosphate dehydrogenase deficiency may suffer from neonatal jaundice. In rare cases, even the kidneys may fail completely. Generally, compensatory processes take place in the body, so the hemolytic crisis ends quickly. The prognosis of the disease is good. However, in rare cases, a fatal outcome is possible.
Diagnosis
To diagnose glucose-6-phosphate dehydrogenase deficiency, the physician will first take a medical history. If symptoms such as anemia, jaundice, and hemolysis features occur, glucose-6-phosphate dehydrogenase deficiency is suspected in certain ethnic groups and individuals with a history of cases of the condition in their relatives. Furthermore, laboratory tests for liver enzymes, reticulocyte count, lactate dehydrogenase, haptoglobin, or a direct antiglobin test (Coombs test) are performed. If the Coombs test excludes an immunological cause for the hemolysis, the suspicion of a glucose-6-phosphate dehydrogenase deficiency is strengthened. NADH can be detected directly via the so-called Beutler test. If no fluorescence of the blood cells is observed, this means a positive Beutler test. Thus, the diagnosis of glucose-6-phosphate dehydrogenase deficiency can be confirmed.
Complications
Glucose-6-phosphate dehydrogenase deficiency does not necessarily lead to complications or symptoms in every case. For example, the deficiency occurs even when there are active enzymes. However, if this is not the case, glucose-6-phosphate dehydrogenase deficiency can also lead to the death of red blood cells. This death has relatively severe consequences and symptoms similar to a common fever. It results in fever, aching limbs and chills. Likewise, the abdomen and back may also be affected by pain, resulting in a severe restriction of the patient’s daily life. The quality of life decreases drastically due to the glucose-6-phosphate dehydrogenase deficiency. In the worst case, renal insufficiency occurs, which can even lead to death. Infants may also develop jaundice due to the deficiency. If glucose-6-phosphate dehydrogenase deficiency is triggered by a drug or food, the affected person must stop taking it. In most cases, this does not lead to further complications. A causal treatment is not possible. If the deficiency can be corrected, there is no reduction in life expectancy.
When should you see a doctor?
People who have relatives in their family who have glucose-6-phosphate dehydrogenase deficiency should have a genetic test performed for clarification. If symptoms such as chills, aching limbs or fever occur, there is cause for concern. The flu-like symptoms must be checked by a doctor. If the symptoms persist unabated for several days, a doctor must be consulted. General weakness, pain in the back, or abdominal pain should be investigated and treated. Increased fatigue, exhaustion or inner restlessness should be clarified by a physician. If shock occurs, a doctor should be consulted immediately. In severe cases, an ambulance service must be informed. The instructions of the emergency personnel must be followed until they arrive. Discoloration of urine is considered unusual. In case of black discoloration, a doctor must be consulted as soon as possible. A visit to the doctor is also necessary in case of yellow discoloration of the skin. If kidney complaints occur, a check-up visit to a doctor is recommended. If there is kidney dysfunction, pain or a decrease in performance, a doctor is needed. If fluid intake is refused due to discomfort, a doctor’s visit is required because dehydration is imminent. In the event of kidney failure, an emergency physician must be called. There is a danger to the life of the affected person.
Treatment and therapy
Currently, there is no causative therapy for glucose-6-phosphate dehydrogenase deficiency. In acute hemolytic anemia, blood transfusion may be necessary. Otherwise, therapy consists of avoiding favism-inducing foods and agents. These include beans (mainly fava beans), peas, currants, vitamin K, acetylsalicylic acid, sulfonamides, naphthalene, and aniline derivatives.If these triggers are avoided, no symptoms occur. Life expectancy is not reduced in glucose-6-phosphate dehydrogenase deficiency.
Outlook and prognosis
Glucose-6-phosphate dehydrogenase deficiency is a genetic disorder. Because human genetics cannot be altered for legal reasons, there is no cure for the disorder. Therapy is therefore aimed at alleviating the symptoms. A large number of patients do not experience any impairments despite the diagnosed disorder. They do not experience any abnormalities or complaints in the course of their lives. The prognosis is therefore very favorable in them and treatment is not necessary. However, the affected person should undergo regular check-ups so that a rapid response can be made in the event of changes or peculiarities. Normally, the focus of medical care is on reducing the discomfort caused by the deficiency. The prognosis is favorable if the patient adheres to certain guidelines. In a well-prepared treatment and therapy plan, the aim is to improve health. If the patient adheres to a special diet plan, there is significant relief of symptoms. Priority should be given to avoiding the intake of certain foods. In particular, beans, peas or currants should be eliminated from the diet plan for a good prognosis. If they are consumed, the irregularities increase again in a short time. The diet must be followed for life to strengthen the well-being and promote the health of the patient.
Prevention
Because glucose-6-phosphate dehydrogenase deficiency is hereditary, there is no way to prevent it. Only the symptoms of hemolytic anemia can be prevented by avoiding triggering substances.
Follow-up
Special options for aftercare are usually not possible or necessary in glucose-6-phosphate dehydrogenase deficiency. In this case, the affected person is primarily dependent on direct treatment of this complaint to prevent further complications. Early diagnosis in particular has a very positive effect on the further course of the disease and can help to alleviate the symptoms. Life expectancy is often not negatively affected by this disease. In glucose-6-phosphate dehydrogenase deficiency, the patient is dependent on taking medications and other supplements to alleviate the symptoms. Likewise, agents that trigger the discomfort should be avoided as much as possible to spare the body. When taking the medicines, care should be taken to ensure that they are taken regularly. Possible interactions with other medications should also be taken into account, and the doctor can also be asked for advice. The doctor can also provide the sufferer with a diet plan to ensure a proper diet. If the symptoms of glucose-6-phosphate dehydrogenase deficiency are severe, it is better to call an emergency doctor or go directly to the hospital. Contacting other sufferers of glucose-6-phosphate dehydrogenase deficiency may also be useful in this regard, as it will lead to an exchange of information, which may be helpful for everyday life.
Here’s what you can do yourself
In most cases, glucose-6-phosphate dehydrogenase deficiency can be treated relatively well by the affected person avoiding certain foods. This can limit most of the symptoms, so that direct medical treatment is not always necessary either. However, a diet plan is always suitable here, which can also be drawn up with a nutritionist. In an acute emergency, the glucose-6-phosphate dehydrogenase deficiency is usually compensated by a blood transfusion. As the condition progresses, the affected person should avoid beans and peas in his or her diet. Currants or vitamin K also have a negative effect and can promote the disease. Likewise, the patient should not take aspirin or aniline derivatives. If these ingredients and foods are avoided, the symptoms of glucose-6-phosphate dehydrogenase deficiency can be completely treated. In many cases, contact with other patients of the disease also has a very positive effect on the further course, whereby an exchange of information can occur. With a strict diet, the symptoms do not reappear, so that blood transfusions are not necessary.Usually, abstaining from the triggering foods does not have a particularly negative effect on the patient’s quality of life.
