The Alpha Thalassemias

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Offline Andy Battaglia

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The Alpha Thalassemias
« on: June 07, 2008, 09:10:00 PM »
Alpha thalassemia is a disorder of the gene which is responsible for the production of the alpha globin that combines with beta globin to make hemoglobin. In a normal individual, these two globins are produced in equal amounts resulting in normal hemoglobin. In the thalassemias, some mutation or deletion prevents these genes from functioning properly, resulting in some degree of thalassemia. In alpha thalassemia, there are four alpha producing genes involved. The most common cause of any of the alpha thals is a total deletion of one or more of the alpha genes, resulting in an imbalance of the ratio of beta and alpha globins. When one or two of the alpha genes are deleted, it is very difficult to detect and usually goes unnoticed. This makes keeping a family history of this disorder very important since severe problems can arise when an alpha trait carrier has children with another alpha trait carrier.

There are four basic types of alpha thalassemia, depending on how many of the alpha genes are deleted.

One gene deleted results in alpha thal silent carrier state. Individuals who are silent carriers normally exhibit no problems and no reduction in hemoglobin level. There may be mild reductions in red cell mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Typically, silent carrier state is not discovered unless there is a prior family history or the silent carrier has children with another alpha thal carrier and a more severe condition results because the child has inherited alpha thal genes from both parents. The most important concern with silent carrier is when it is combined with a two alpha thal gene parent and the child inherits three alpha thal genes.

Two gene deletion results in alpha thalassemia trait. This is called alpha thal minor. It may result in a mild anemia, reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Affected individuals may find some help with daily folic acid supplements. The real danger with alpha thal minor comes when having children with another alpha thal carrier, which has the potential to result in 3 or 4 gene deletion alpha thal. Family history and genetic counseling are very important when alpha thal trait is suspected. Those who know that thalassemia is found in their families have a responsibility to inform their families about this trait so that proper precautions can be taken when deciding to have children.

Three gene deletion means that only one of the alpha globin genes in functional. This results in HbH disease, which is quite variable in symptoms. Some with HbH have moderate anemia that does not require transfusions and some become transfusion dependent because their hemoglobin level is too low to maintain good health. HbH is similar to beta thal intermedia in some respects because of this wide variation in condition. Typically patients have moderate anemia that may worsen as they age, leading to transfusion dependence in the second or third decade of life. Some with HbH will never need to transfuse, although it may be occasionally necessary during times of illness or physical stress. Those with HbH should avoid oxidants, chemicals and foods such as sulfa drugs, benzene, and fava beans, as they can all stimulate increased hemolysis (destruction of red blood cells). Daily folic acid supplements are the main course of treatment for non-transfusing alpha thals. Care should be take to avoid oxidant food and drugs and regular medical monitoring and treatment is necessary. Hemoglobin H has a high oxygen affinity which means it does not let go of oxygen as easily as normal hemoglobin, so Hb levels may be misleading. Transfusion should be based on physical condition rather than depending on Hb levels as the Hb may seem higher than it functionally is for the patient. Iron absorption from food is not a big problem for alpha thals normally but those who transfuse must undergo chelation treatment, just as transfusing beta thals. Iron supplementation should be avoided as it can add to the iron load and will not help the condition. Splenectomy is often used in transfusing patients to help reduce transfusion frequency. Infections should always be attended to promptly, especially if splenectomy has already occurred. Infection can lead to lower Hb, the same as seen in beta thal, so it should always be taken seriously and dealt with promptly, to avoid any further problems. HbH patients with low Hb may develop the same skeletal abnormalities seen in beta thal and transfusion is an option to help avoid this. Because HbH involves three deleted alpha genes, it is not recommended to have children with another alpha trait carrier, as the chances for severe problems in the children are significant. Genetic counseling is highly recommended.

Hemoglobin H-Constant Spring is also a three gene affected alpha thalassemia but it involves at least one of the alpha genes being mutated rather than deleted. This condition is a more severe thalassemia usually, often resulting in transfusion dependence. An Hb of only 7-8 is common and splenectomy is often performed to allow red blood cells to survive longer. However, splenectomy can lead to further complications such as clotting issues and a hypercoagulable state, in which clotting occurs more easily. If this is an issue it may be dealt with by taking blood thinners. These may be simple like vitamin E or daily aspirin or even drugs like heparin, especially if a surgery is ever required.

Alpha thalassemia major is also known as hydrops fetalis and is caused by a deletion of all four alpha globin genes. Without any alpha globin, no adult hemoglobin can be produced and the fetus normally dies during the pregnancy or is stillborn. In some rare cases, in utero transfusions have saved alpha major babies. The hope is that more of these babies can be diagnosed in the uterus and preemptive transfusions can begin.

Alpha thalassemia is difficult to detect in its carrier stages but if suspected, it can be verified by DNA testing.The importance of passing on the family history cannot be stressed enough. While carrier state is usually not noticed, when combined with another carrier, the result can be alpha major and death. Carriers need to be educated about this possibility.

As with beta thalassemia, it will serve the patient to have a good lifestyle. Proper diet and supplements, avoidance of junk foods, alcohol and tobacco and mild to moderate exercise can all be keys to optimizing health. Junk foods not only don't add nutritional value but they also deplete vitamins and minerals from the body as it processes them. Eat well and live well.

All we are saying is give thals a chance.


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