Günther’s disease is an autosomal recessive inherited gene mutation of chromosome ten. The disease disrupts enzyme activity and the biosynthesis of heme into red blood pigment. Anemia and photosensitivity are among the major symptoms.
What is Guenther’s disease?
Günther’s disease is understood by physicians to be a rare inherited disorder. The disease is also known as congenital erythropoietic porphyria. It disrupts the biosynthesis of the iron-containing pigment in red blood cells. This pigment is also known as heme. Together with globins, heme forms hemoglobin in healthy humans. Red blood cells contain hemoglobin for oxygen transport. The diseases must be distinguished from porphyria and transfusion reaction. Both can cause similar symptoms and are therefore important for differential diagnosis. In some cases, diseases resulting from uranium-containing ammunition are also referred to as Günther’s disease. However, this is not technically correct and is not related to the real Günther’s disease. Nor is there any connection between Günther’s disease and xeroderma pigmentosum. This disease causes similar symptoms. In this case, however, the cause is a genetic regeneration disorder of the skin cells.
Causes
The cause of Guenther’s disease is a genetic defect. Usually, it is a defect of chromosome ten. This chromosome encodes an enzyme involved in porphyrin metabolism. The enzyme is also called uroporphyrinogen III synthase and is found in all tissue types in healthy humans. In the biosynthesis of heme and globin, the body requires this uroporphyrinogen III synthase in addition to a total of seven other enzymes. In most cases, Günther’s disease is inherited via autosomal recessive inheritance. Both partners must carry the defective gene. However, the presence of the gene defect does not necessarily cause the actual onset of the disease. Thus, two partners with the defect may eventually father a child without the defect. The probability of this scenario is the same as that of fathering a child with the disease. However, the risk for children with the unaffected genetic defect is twice as high.
Symptoms, symptoms, and signs
The first symptoms of Guenther’s disease usually manifest in early childhood. In most cases, dermal symptoms appear first. Patients’ skin is generally more sensitive to light than that of healthy individuals. This light intolerance is associated with the accumulation of the heme precursor uroporphyrinogen I. This accumulation results in the inability to synthesize heme for further processing. As a result, the skin of patients with Günther’s disease tends to show redness and vesicles. These phenomena sometimes turn into ulcers. In later stages of life, hyper- or hypopigmentation sometimes appears on the skin and conjunctiva. Equally symptomatic of the disease is red or pink urine. Patients’ teeth are often brownish or reddish-brown and fluoresce long waves under UV light. Splenomegaly, hemolytic anemia, and skin cancer are possible late effects of the disease. Sometimes, apart from the above symptoms, patients exhibit intolerance to garlic. For this reason, anemic Günther’s disease is now thought to be the origin of the vampire myth.
Diagnosis and course of the disease
The first clue to Günther’s disease is given to the physician by reddish or brownish discolored urine. In most cases, this discoloration can be observed shortly after birth. Especially for newborns with jaundice, early diagnosis can be crucial. Neonatal jaundice is often treated with light therapies. However, newborns with Günther’s disease would suffer severe burns in such light therapy. Since even defect-bearing parents do not have the disease in most cases, family history plays a minor role in the diagnosis of the disease. Detection of uroporphyrinogen I in urine can be done by HPLC and is considered diagnostic. The prognosis for Guenther’s disease is considered unfavorable, with limited treatment options available to date.
Complications
In most cases, the symptoms of Günther’s disease occur at a very young age. In this case, the children primarily suffer from light intolerance and can thus also develop visual problems or complete blindness.Blisters and redness appear on the skin of patients, which can severely limit the aesthetics of those affected. Children in particular can suffer from teasing and bullying, which can result in mental illness. Furthermore, the teeth of Günther’s disease are also affected, resulting in brown discoloration of the teeth. Likewise, the risk of the patient developing skin cancer increases, so that those affected are dependent on regular examinations by a doctor. The patient’s quality of life is significantly reduced and limited by Günther’s disease. A causal treatment of Günther’s disease is not possible. Patients are therefore dependent on various therapies and must protect their skin from burns. Particular complications do not occur in most cases.
When should one go to the doctor?
Changes or abnormalities in the appearance of the skin should be examined and treated by a doctor. If irregularities and peculiarities of the skin already occur in children, a pediatrician should be consulted. Strong sensitivity to the effects of light is considered a warning sign of the organism and should be clarified. The formation of blisters, redness of the skin or pain are signs of health impairment. A doctor should be consulted as soon as the complaints persist over a longer period of time or increase in intensity. In case of swellings or ulcers on the organism, action is required. They are of particular concern if they increase in size or spread over the body within a short period of time. Discoloration of the urine or teeth also indicates a disorder. Once urine is repeatedly pink and not triggered due to physical exertion, medical attention is needed. Slightly brownish teeth are also considered unnatural and should be presented to a doctor. In case of a general feeling of illness, inner restlessness or diffuse changes in the organism, a visit to the doctor is advisable. If emotional or mental inconsistencies occur in addition to the physical symptoms, a doctor is needed. In case of mood swings, behavioral abnormalities as well as a withdrawal from social life, a visit to the doctor is advisable. Children often show a whiny demeanor during prolonged exposure to light.
Treatment and therapy
For the treatment of Günther’s disease, almost exclusively general measures are available to treat the symptoms. Among these, protection from sunlight is most important. This protection is intended to prevent burns and reduce patients’ increased risk of skin cancer. Operatively, an allogeneic stem cell therapy can be considered as a treatment measure. In this case, the stem cells of another person are transplanted into the patient. However, such surgery carries high risks and sometimes does not lead to the desired success. The body’s immune system often initiates violent defense reactions because of the stem cells that are recognized as foreign. These reactions can be suppressed by immunosuppressants. However, patients with Günther’s disease must maintain the drug therapy with immunosuppressants for the rest of their lives after the stem cell transplantation. It also makes them permanently more susceptible to general diseases. In the meantime, medicine is also experimenting with causal surgical procedures for the causal therapy of the disease. The first gene therapies on living humans have already been successful in the context of other diseases. However, deaths have also occurred in gene therapy trials in the past. However, gene therapy is currently (as of 2015) still one of the main areas of current research in medicine.
Outlook and prognosis
Günther disease offers an unfavorable prognosis. CEP is a severe disease that presents with a life-threatening symptom pattern and leads to death in a large proportion of affected children. To date, no causative therapy exists. An improvement of the symptoms can be achieved by the strict avoidance of sunlight as well as the intake of medications such as beta-carotene. For this, treatment must be initiated at an early stage. Severe diseases can be treated in some cases by means of stem cell therapy. Early diagnosis can improve the prognosis. The quality of life of children with the disease is greatly reduced. Life expectancy is also limited, as anemia and carcinoma inevitably cause discomfort and significantly limit the patient.For the relatives, the child’s illness represents a considerable burden. As a rule, they need therapeutic support. The affected child must also be supported, especially in severe courses that are physically and emotionally stressful. Well-being can be improved by the administration of painkillers and other medications. The prognosis for Günther’s disease is made by the pediatrician in charge or a specialist for genetic diseases. For this purpose, he will take into account the symptom picture, the patient’s constitution and a number of other factors.
Prevention
As an autosomal recessive hereditary disease, Guenther’s disease cannot be prevented. However, DNA sequence analysis can help expectant parents or couples in family planning assess the risks of disease in their offspring.
Follow-up
As a general rule, patients suffering from the rare hereditary disease Günther’s disease must strictly avoid sunlight. Spending time outdoors is possible during the day and with appropriate protective measures. Normal suntan lotion is unsuitable for precautionary purposes, as these products filter out the UVA and UVB components of light but allow blue light to pass through. Therefore, affected individuals rely on mineral-based sunscreens and special protective clothing that covers the entire body. Since the hematopoietic system does not function properly in Günther’s disease, a monthly blood transfusion is required. The genetic defect is associated with changes in the teeth, so regular checkups and treatment with a dentist are recommended. Meanwhile, some patients with Günther’s disease receive a bone marrow transplant to treat the condition. In this case, lifelong use of medications that suppress the immune system and prevent rejection is required. The first year after transplantation is particularly critical because the body’s immune system needs this time to regenerate. Therefore, patients are susceptible to infections of all kinds. To minimize the risk, contact with animals, plants, plant soil or compost should be avoided. Large gatherings of people are also critical. Further behavioral tips are provided by the attending physician.
This is what you can do yourself
If Günther’s disease has been diagnosed, those affected must first and foremost avoid sun exposure. It is recommended to wear suitable protective clothing outdoors. The face and eyes can be protected by special protective masks as well as suitable sunglasses. If skin symptoms nevertheless occur, the doctor must prescribe a suitable preparation. If necessary, remedies from alternative medicine as well as various home remedies can also be used. This is particularly recommended in the case of severe skin changes associated with itching, bleeding and other complications. If the defective cells are not treated early, scarring can develop. Since these are often also mentally stressful, treatment must be given in any case. If the permanent skin changes put a strain on the psyche, psychological advice should be sought. Günther’s disease can be effectively alleviated by self-help measures. Nevertheless, comprehensive medical treatment is always necessary. Particularly in the later stages of the disease, severe metabolic disturbances can occur that cannot be alleviated independently and sometimes have an impact on the psyche and the entire body. In this case, a suitable treatment concept should be worked out together with the physician. Taking the prescribed medication regularly is essential for a speedy recovery.
