α-thalassemia
| Classification according to ICD-10 | |
|---|---|
| D56.0 | Alpha thalassemia |
| ICD-10 online (WHO version 2019) | |
Alpha thalassemia (α-thalassemia) is a form of thalassemia that involves the genes HBA1 and HBA2 . Alpha thalassemia is due to a decreased production of 1, 2, 3 or 4 alpha globin chains, which leads to a relatively high excess of beta globin chains. The degree of the disorder depends on the clinical phenotype or how many chains are affected.
Epidemiology
The worldwide occurrence of inherited alpha thalassemias corresponds to the areas of occurrence of malaria, which suggests a protective role of alpha thalassemias against malaria. This is why alpha thalassemia is very common in sub-Saharan Africa, the Mediterranean, the Middle East, South Asia, and Southeast Asia, and different genetic subtypes have variable frequencies in each of these areas. The epidemiology of alpha thalassemia in the US reflects this global distribution pattern. The most common form of alpha (+) thalassemia seen in the United States is the alpha (3,7) deletion, a single alpha globin gene deletion found in approximately 30% of African Americans. Even in the homozygous state, this disorder manifests itself only in a mild microcytic anemia . Although significantly more severe clinical diseases of HbH and Hb Barts are detected in the US today, the diseases are more common in the western US and have increased in prevalence over the past two decades due to increased Asian immigration.
causes
It is most often inherited recessively and is also related to the deletion of chromosome 16p.
It can also be acquired in rare circumstances. Due to the low incidence of alpha thalassemia, the disease can be confused with iron deficiency anemia.
Pathophysiology
In α-thalassemias, which result from reduced alpha globin production, fewer alpha globin chains are therefore produced, which leads to an excess of β chains in adults and excess γ chains in newborns. The excess β chains form unstable tetramers (hemoglobin H or HbH made up of 4 beta chains) that have unusual oxygen dissociation curves . The excess γ chains form tetramers, which are poor O 2 carriers because their affinity for O 2 is so high that it is not dissociated in the periphery . Homozygous α 0 thalassemias, in which there are many γ 4 globins but no α globin at all (Hb Barts), often lead to stillbirths .
Types
There are two genetic loci for α-globin and therefore four genes in diploid cells. Two genes are of maternal and two genes are of paternal origin. The severity of α-thalassemia depends on the number of α-globin genes affected: the more, the more severe the symptoms of the disease.
The genotype a “-” indicates a lack of function; a "α", however, stands for a functional alpha chain.
| affected alleles | description | genotype |
|---|---|---|
| one | There is minimal impact. Three α-globin genes are sufficient to allow normal hemoglobin production so that there are no clinical symptoms. They are called "silent carriers". You can slightly reduce the mean individual erythrocyte volume and the mean corpuscular hemoglobin . | - / α α / α |
| Two | The condition is known as an "alpha thalassemia trait". Two α genes enable almost normal erythropoiesis ; however, there is mild microcytic hypochromic anemia . In this form, the disease can be mistaken for iron deficiency anemia and incorrectly treated with iron.
There are two forms:
|
- / - α / α or - / α - / α |
| Three | This condition is known as "hemoglobin H disease". There are two unstable hemoglobins in the blood: hemoglobin Barts (tetrameric γ chains ) and hemoglobin H (tetrameric β chains ). Both of these unstable hemoglobins have a higher affinity for oxygen than normal hemoglobin, which results in a poor oxygen supply to tissues. This shows a microcytic hypochromic anemia with target cells and Heinz bodies in the blood smear and also a splenomegaly . The disease may first be noticed in childhood or early adulthood when anemia and splenomegaly occur. | - / - - / α |
| Four | The fetus cannot live outside the uterus and may not survive pregnancy: most of the children affected are stillbirths with hydrops fetalis , and those who are born alive die soon after birth. You have edema and low circulating hemoglobin. This remaining hemoglobin has tetrameric γ-chains (hemoglobin Barts). | - / - - / - |
Individual evidence
- ↑ Α thalassemia. In: Online Mendelian Inheritance in Man . (English)
- ↑ Α thalassemia. In: Online Mendelian Inheritance in Man . (English)
- ↑ J. Flint, AV Hill, DK Bowden et al .: High frequencies of alpha-thalassemia are the result of natural selection by malaria. In: Nature. 1986; 321, pp. 744-750.
- ^ LF Bernini: Geographic distribution of alpha thalassemia. In: M. Steinberg, B. Forget, D. Higgs, et al. (Eds.): Disorders of hemoglobin. Cambridge University Press, New York, 2001, pp. 878-894.
- ^ E. Beutler, C. West: Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. In: Blood. 2005; 106, pp. 740-745.
- ↑ EP Vichinsky, EA Macklin, JS Waye include: Changes in the epidemiology of thalassemia in North America: a new minority disease. In: Pediatrics. 2005; 116, pp. 818-825.
- ↑ DP Steensma, RJ Gibbons, DR Higgs: Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies . In: Blood . tape 105 , no. 2 , January 2005, p. 443-452 , doi : 10.1182 / blood-2004-07-2792 , PMID 15358626 .
- ↑ cooleysanemia.org
