A hemoglobinopathy represents a hereditary abnormal change in hemoglobin. The main areas of distribution of hemoglobinopathies are the tropics and subtropics. The expression of each blood disorder depends on the particular genetic defect.
What is a hemoglobinopathy?
Hemoglobinopathies are genetic blood disorders that occur mainly in the tropics and in many Mediterranean countries. About seven percent of the world’s population suffers from some form of hemoglobinopathy. These are mostly autosomal recessive inherited gene mutations. Heterozygous carriers of the respective mutation have a survival advantage against severe malaria infections. While carriers of healthy genes often die of malaria and often do not reach reproductive age, heterozygous carriers are better able to survive severe malaria crises. Thus, the mutant genes that can cause homozygous hemoglobinopathies gain a selection advantage in malarial regions. Because malaria is particularly prevalent in tropical and subtropical areas of the world, nearly 30 percent of the population there has gene predispositions for various hemoglobinopathies. The different mutations also produce different forms of blood diseases. Thus, specific properties of hemoglobin such as oxygen affinity, stability, the ability to aggregate, the tendency to form methemoglobin, or even insignificant features may be altered. Hemoglobinopathies can basically be divided into two broad categories. These are thalassemias on the one hand and abnormal hemoglobins on the other. Among the thalassemias, there are mainly the alpha and beta thalassemias. The gamma and delta thalassemias occur less frequently. Hemoglobin is an iron-containing protein complex of four globins (from alpha to delta globin).
- Beta-thalassemias are the most common, which in turn are divided into the milder beta-thalassemia minor and the more severe beta-thalassemia major.
- In the alpha-thalassemias, there is the clinically silent alpha-thalassemia minima, the mild alpha-thalassemia minor, the more severe alpha-thalassemia major/HbH disease and Hb-Bart’s disease with the most severe course.
- The best known hemoglobinopathy with abnormal hemoglobin is the so-called sickle cell anemia.
Causes
Hemoglobinopathies are due to various gene mutations. For example, in beta thalassemias, approximately 4000 mutations are known to cause changes in beta globin. The responsible gene is located on chromosome 11. In alpha thalassemias, approximately 55 gene mutations have been uncovered to date. The corresponding gene is located on chromosome 16. The best known abnormal hemoglobin is formed in the so-called sickle cell anemia. The cause of this disease is a point mutation on chromosome 11, which is the same gene responsible for coding beta-globin. Here, instead of glutamic acid, the amino acid valine is located at position six of the beta-globin protein subunit. This makes the beta-globin chain unstable. This instability leads to a crescent-shaped deformation of the red blood cells at low oxygen partial pressure. Although the hemoglobin retains the ability to bind oxygen. However, the breakdown of the beta-globin chain poses the risk of aggregation of the blood cells with the formation of blood clots. The blood dissolves very rapidly releasing free hemoglobin, arginase and oxygen radicals. As a result, nitric oxide is consumed more. Since nitric oxide is responsible for the dilation of blood vessels, its shortage leads to their constriction.
Symptoms, complaints, and signs
The thalassemias offer a highly variable clinical picture. Alpha-thalassemia minima shows no symptoms at all. Affected individuals are merely heterozygous gene carriers. Thalassemia minor also shows hardly any symptoms. Only mild anemia is observed. Moderate anemia occurs in the intermedia form of thalassemia and severe anemia in the major form. Other symptoms include icterus (jaundice) due to increased hemolysis, enlargement of the spleen (splenomegaly), or a severe strain on the heart. Affected children suffer from growth disorders, bone malformations and severe impairment of the internal organs.Anemia is characterized by reduced performance, fatigue, headaches, increased heart rate and dizziness. The immune system is generally weakened, resulting in frequent infections. In sickle cell anemia, oxygen deficiency with breathing difficulties, frequent infections, dehydration, hyperacidity of the body (acidosis), and hemolysis are prominent. Infarctions of internal organs can occur as serious complications. The life expectancy of patients is severely limited.
Diagnosis and course of the disease
After a tentative diagnosis based on typical symptoms, hemoglobinopathies can be clearly diagnosed by chromatography or hemoglobin electrophoresis.
Complications
Hemoglobinopathy can cause a variety of complications and symptoms. In most cases, anemia occurs and the patient cannot undergo high levels of stress or activity. Likewise, most affected individuals suffer from jaundice and growth disorders, which can lead to complications, especially in children. The internal organs may also be affected by malformations. Fatigue sets in and the patient’s performance is often impaired. It is not uncommon for nausea and dizziness to occur, and the patient feels ill and unresponsive. Due to the weakened immune system, illnesses and infections also occur frequently. As the disease progresses, the respiratory tract may become inflamed, which can be a life-threatening situation for the patient. Hemoglobinopathy is usually treated causally. Complications do not occur. In most cases, blood transfusions or stem cells are used to limit the symptoms of hemoglobinopathy. However, it is not successful in every case. Life expectancy may be limited if certain damage or organ malformations have already occurred.
When should you go to the doctor?
Symptoms such as jaundice, fatigue, and dizziness must be promptly evaluated by a physician. If hemoglobinopathy is not treated, serious complications can develop. Therefore, medical advice should be sought at the first sign of disease. If severe headaches, abnormal posture or breathing difficulties develop, this must be clarified by the family doctor and treated if necessary. If infections occur due to the weakened immune system, the affected person must consult a doctor immediately. Inflammation of the respiratory tract, persistent dizziness and high fever are further warning signs that require treatment. In the case of pneumonia, an examination at the nearest hospital is necessary in any case. Parents who notice symptoms in their child such as growth disorders, organ dysfunction or bone malformations should inform the pediatrician. The physician can make an initial diagnosis and, if necessary, refer the parents to a specialist clinic for hereditary diseases. Other contacts are specialists in internal medicine as well as therapists. Depending on the symptom picture, a nutritional physician and a pulmonary specialist may also be involved.
Treatment and therapy
Hemoglobinopathies are hereditary disorders and are therefore usually treated only symptomatically in milder courses. Treatment includes prevention of infection and dehydration (desiccosis). Pain is treated with analgesics if necessary. In the case of an aplastic crisis, blood transfusions are necessary. More severe forms of hemoglobinopathies often lead to early death. Here, causal therapies leading to cure also become necessary. Stem cell transplants or allogeneic bone marrow transplants are suitable for this purpose. Moderate to severe thalassemia, for example, requires regular blood transfusions every two to four weeks. This is to prevent severe anemia. Unfortunately, the lifelong need for blood transfusions also leads to overloading the body with iron. Therefore, iron binders must also be administered periodically parenterally by infusion or perorally by tablets to eliminate the iron from the body. For causal treatment of sickle cell anemia, research is currently being conducted to correct the gene mutation. However, it is too early to find a viable solution.
Prevention
Because the hemoglobinopathies are genetic, there is no recommendation for its prevention.If there is a history of congenital blood disorders in the family or relatives, their cause should be determined and human genetic counseling should be sought if children are desired.
Follow-up
In most cases, affected individuals with hemoglobinopathy have very few, if any, specific measures of direct follow-up available to them. First and foremost, it is important to diagnose the disease quickly and, above all, at an early stage to prevent further complications or symptoms. The earlier hemoglobinopathy is detected and treated, the better the further course of the disease in most cases. Most patients are dependent on taking various medications for this disease. It is always important to ensure that the medication is taken regularly and in the correct dosage so that the symptoms can be properly alleviated. Likewise, a doctor should be consulted first if there are any questions or if anything is unclear. Sometimes bone marrow transplants are also necessary so that the affected person can survive. Intensive and loving conversations with one’s own family or friends are also often necessary, as this can prevent psychological complaints or even depression in particular. Frequently, contact with other sufferers of hemoglobinopathy is also very useful, as this can lead to an exchange of information.
What you can do yourself
It is not possible to treat hemoglobinopathy by self-help means. For this reason, in any case, those affected by this disease are dependent on symptomatic treatment by a doctor, which is usually carried out with the help of blood transfusions. If the hemoglobinopathy is supported with the help of medications, the affected person should always make sure to take the medications regularly. The blood transfusions will prevent anemia. Ideally, the patient should refrain from heavy and strenuous activities in order not to put unnecessary strain on the body. Furthermore, the permanent blood transfusions can lead to high iron levels in the body. In order to prevent possible discomfort and complications caused by this high content, those affected depend on taking iron binders. Likewise, foods rich in iron should be avoided in everyday life. In many cases, contact with other sufferers of hemoglobinopathy is also helpful, as this can lead to an exchange of information that can make everyday life easier and improve the patient’s quality of life. In the case of psychological limitations, conversations with familiar people are often very helpful.