There are two types of globins that combine to produce the main hemoglobin found in red blood cells. These are alpha and beta hemoglobin and their production depends on the alpha and beta hemoglobin genes, respectively. The beta thalassemias are a group of blood disorders in which the function of one or both beta hemoglobin genes are affected. Generally, if one beta gene is affected, thalassemia minor is the result. If both beta hemoglobin genes are affected, the result is thalassemia intermedia or major, depending on how severely the gene is affected. Genes can be mutated or even completely deleted. At times there are also other genetic factors that can affect the severity of the thalassemia.
Thalassemia MinorWhen one has thalassemia minor, it means that one of the two beta hemoglobin genes inherited from the parents, is defective. There are hundreds of different known mutations of the beta hemoglobin gene, with more constantly being discovered. There is one simple fact about thal minor that cannot be ignored. In beta minor, one of the two beta globin genes is affected by mutation or deletion and this gene often cannot produce an adequate amount of beta globin to mix with alpha globin to form hemoglobin and this can result in a low Hb level and anemia. The extent of the mutation has much to do with the ultimate symptoms a patient will experience. Complete deletion of the gene is called beta zero, and the result is usually a more severe anemia than most minors will experience. In some rare cases, blood transfusions may be required. For most minors, transfusions are never required, although some thal minor women may need blood during pregnancy, so regular monitoring of hemoglobin levels are recommended.
Thalassemia minor is also called thalassemia trait or carrier. It can usually be detected by a test called the hemoglobin electrophoresis test. Sometimes even this test does not show the trait so DNA testing is done to verify whether or not one is a carrier. Once carrier status is verified, it is extremely important that the patient is made aware of what this means in terms of having children. When two carriers have a child there is a statistical 25% chance of having a thal major child, so it is very important that carriers have their mate tested before deciding to have children. Genetic counseling is necessary if this is the case, as steps can be taken to avoid having a major child. Do not underestimate the importance of being tested before having children. This group is loaded with parents who wish they had this information before having children.
Thalassemia minor can have many symptoms, even though most articles on the subject will say that minors have nothing more than mild anemia. Unfortunately, this is not true. The effects of minor can be substantial. Many minors have no significant symptoms, but others have many symptoms that greatly affect the quality of their lives. Among the reported symptoms are anemia, tiredness, weakness, numbness in the extremities, hair loss, slow thyroid, low immune systems, feeling cold, lightheaded feeling, and depression. In some cases, enlargement of the spleen and even excess hemolysis (premature destruction of red blood cells) may also be noted.
Most doctors are befuddled about thal minor and give few if any recommendations. Often, doctors mistakenly prescribe iron supplements when they see the low hematocrit level. However, unless iron deficiency coincides with the thal minor, iron will not help and long term usage when not needed can cause problems, including damage to organs.
Iron deficiency should be verified through iron studies, which include the serum ferritin and serum iron tests, before iron supplements are ever taken.Thal minors need to try to optimize their health through diet, supplements and exercise. Minors have very little of the margin of error that non-thals have and have to pay close attention to maintaining good health. Folic acid should be taken by all thal carriers, minor through major. B-complex vitamins can also help energy levels and are needed to build red blood cells. Vitamin E is a good antioxidant that helps protect red blood cells. Magnesium and vitamin D are also of great interest to all thals. Wheatgrass in any of its forms, juice, tablets or extract, may help to raise fetal hemoglobin levels and also improve the immune system and overall energy levels. For a more in depth view of what supplements thal patients should take, please refer to our thread at
http://www.thalassemiapatientsandfriends.com/index.php/topic,4890.msg46774.html#msg46774Moderate exercise is also important as it creates better circulation and a more efficient circulatory system. Walking and swimming are both low impact exercises that can be of benefit. There are great athletes that are thal minors, including tennis great, Pete Sampras and football (soccer) legend, Zinedine Zidane. Being fit is the best treatment for thal minor. Try to optimize what you do have. There is no magic cure for the ailments found in thalassemia minor but patients can help themselves by leading a healthy life and understanding the body's need for rest. And please let your doctors know that you feel your symptoms are related to thalassemia. The more that doctors hear this, the more likely they are to begin taking thal minor seriously and stop writing it off as hypochondria. If your doctor does not believe that thal minor can negatively impact your life, please refer this site. There are many posts by minors and their quality of life issues and it may help to show your doctor that you are not alone, nor are you imagining your symptoms. With some effort, thal minors can make a significant impact on the quality of their lives.
Thalassemia IntermediaTechnically, thalassemia intermedia refers to a patient, who is able to maintain a hemoglobin level in the 6-8.5 range without taking blood transfusions. Most cases of beta thalassemia intermedia are the result of two defective beta hemoglobin genes, although some rarer cases are the result of the seldom seen dominant thalassemia gene and some are cases of thal beta zero. Usually, intermedia is the result of at least one of the gene mutations being of a "milder" variety, that enables the patient to still produce some useful hemoglobin. Many intermedia patients do not require transfusions when younger, but eventually need to begin regular transfusions. Some doctors will reclassify a patient as major once regular transfusions begin. In recent years it has been noted that starting a program to induce fetal hemoglobin in intermedias when young can help them avoid transfusions later in life. Intermedia can also occur when two beta thal genes are present along with alpha thalassemia trait. The reduced production of alpha hemoglobin is a better match with the reduced production of beta hemoglobin and the result is intermedia rather than major, as the alpha thal acts to moderate the beta thal.
The decision to transfuse in intermedia is based on a combination of hemoglobin levels and bone development. If the low blood supply severely impacts bone growth in children, either transfusion or fetal hemoglobin inducing drugs are recommended. Chief among these drugs are hydroxyurea and butyrate. Current research into drugs related to butyrate hold great promise for the future for thal intermedias and majors. The goal of these drugs is to turn the gene back on that regulates the production of the gamma hemoglobin that combines with alpha hemoglobin to produce the fetal hemoglobin that the body uses until about six months of age. In addition to the drugs, many patients have some degree of success in raising fetal hemoglobin levels by using natural products like wheatgrass and resveratrol, which is derived from red grapes. Both substances are known to increase fetal hemoglobin levels in many patients, enabling them to maintain Hb levels that do not require transfusion. If fetal hemoglobin production cannot be induced by these drugs or supplements, and the Hb level of the patient drops below 7, blood transfusions will most likely be needed.
Intermedia patients require regular medical treatment and observation. Some common problems are enlarged spleen and excess absorption of iron in the gut, slow or inadequate bone development, decreased stature, endocrine system problems and a low immune system. Some of these problems can be alleviated with transfusions but transfusions bring a whole new set of problems and are avoided whenever possible. Often, removal of the spleen is done to eliminate the filtering out of red blood cells by the spleen. The spleen sees the irregular red blood cells found in thalassemia as being defective, and removes them. With splenectomy, this can be reduced but it doesn't work for all patients and some patients eventually return to the same low blood state that they had before the splenectomy. The decision to transfuse in thalassemia intermedia should never be taken lightly and all other avenues should be explored first. However, there may come a time when the quality of life issues outweigh the problems related to transfusion, and the patient will find better health with transfusions.
Intermedias often find themselves with a condition of iron overload even though they don't transfuse. Simply put, because the body is somewhat starved for blood, the bone marrow becomes overactive trying to produce red blood cells (many of which have no useful function) and a mechanism in the gut causes too much iron to be absorbed from food in order to supply iron to these new red cells. Because iron overload is not a normal condition, the body does not use these iron stores to feed the new red cells, but rather uses the normal system of absorbing iron from food. After some years, this can create a dangerous iron overload condition that can damage the organs and destroy the health. Once this occurs, iron chelating drugs are used to reduce this iron load. To limit the amount of iron absorbed, intermedias should drink tea with meals and avoid citrus and vitamin C with meals. Tea inhibits the absorption of iron from food and vitamin C increases it. Foods containing C can still be used by intermedias in moderation but should be taken as snacks between meals. The natural supplement IP6 (phytic acid) which is a member of the B complex family, is a natural iron chelator and can help reduce iron concentrations in the cells and also act as a powerful antioxidant which can help prevent some of the damage that iron does at the cellular level. For maximum effectiveness, take IP6 on an empty stomach and take it with Inositol, a related B vitamin. Raising the Hb level will also help reduce the amount of iron absorbed in the gut, so fetal hemoglobin inducers should also be considered.
It should be remembered that thalassemia intermedia is a classification and genetically, there is little difference between intermedias and majors. Intermedia is basically a more moderate form of major, and much of what applies to majors also applies to intermedias. Intermedia may not be apparent as early as major is but will normally be discovered in the first few years of life, possibly after a "failure to thrive" medical diagnosis.
Thalassemia MajorIn beta-thalassemia major, both beta hemoglobin genes are affected by mutation or deletion, resulting in the production of little if any, useful hemoglobin. Because of this, thal majors cannot survive without regular blood transfusions. Thalassemia major is normally diagnosed within the first year of life. In many cases, it is now being diagnosed in the first few months of life. This early diagnosis is a shock to parents but also the opportunity to begin a treatment program as early as necessary. Over the past 40 years we have seen much progress in the treatment of this blood disorder. Without transfusions, patients lived only a few years but transfusion changed that drastically. Transfused patients could live into their late teens or early twenties, but still did not survive into adulthood, because each transfusion adds a significant amount of iron to the body. Over years, this iron accumulates, as the body has no natural way to remove excess iron. Eventually, the iron builds to toxic levels that render the organs weak and to finally fail. With the advent of iron chelating drugs, this has all changed. Patients who comply with treatment are now living into their 50's and even 60's. No one really knows what to expect as the oldest thals alive today did not have chelation available to them when they were young. Patients born since chelation became part of the routine treatment can expect to live much longer than the thals of earlier periods. Continuing advancements in treatment and the possibility that a cure is on the horizon, make the future look even brighter for thalassemia majors. Where the condition was once a death sentence, it is now considered to be a manageable chronic condition, where patients can lead fairly normal lives. When one first learns about thalassemia it is very important to understand it from this perspective, as advancements have happened relatively quickly and will continue to happen at an even faster rate. New technologies offer hope of artificial blood substitutes, fetal hemoglobin inducing drugs and a gene therapy cure. None of these are theoretical but are actually in the beginning of trial stages in humans. Further research into turning on genes in the body to produce hemoglobin and turning off the mechanism that causes the body to absorb excess iron, are currently taking place. The point is, that when a new parent comes here to read about and understand thalassemia, that hopefully the parent can gain the knowledge that thalassemia is not the hopeless untreatable condition that it was formerly. Great strides are being made in treatment and patients can live normal lives. Read this with hope, as the patient born today has much better treatment and so much to look forward to in the future.
The basic treatment for thalassemia major is a routine of regular blood transfusions and the use of iron chelating drugs to remove the iron that builds up from repeated transfusions. Because the body cannot produce enough hemoglobin to survive, patients need to take regular blood transfusions. Although there are still some problems with using blood that is foreign to one's own body, transfusions are far safer than in previous years. With the advent of testing for HIV during the 80's and hepatitis C during the 90's, two of the biggest problems with transfusions have been abated. The process of matching blood for antibodies is becoming understood better and as a result recipients will see fewer antibody reactions. With each transfusion, more iron enters the body, as the hemoglobin molecules contained in red blood cells contains an iron atom in the center of the molecule. Since the body has no natural method of removing excess iron, a slow build up of iron to toxic levels occurs. Eventually, this iron will destroy the organs unless something is done to remove the iron. Iron chelating drugs have proven to be the answer. These drugs are administered either subcutaneously, using a needle inserted under the skin and a drug pumped in over stretches of 10-12 hours or through newer oral chelating drugs, or some combination of both. This will be discussed at more length in another post. Through the use of chelation and comprehensive care, thalassemia major patients are now living into their 50's and 60's, whereas before the age of chelation they lived into their early 20's at the longest. Chelation changed everything for thals. The newer focus on thal care has become developing treatments for patients who are now much older than what has been the previous experience, and the special health concerns that they, as thals have.
Although a diagnosis of thalassemia major is a serious life changing thing for parents, it is not the disastrous news that it was once. After the intial shock and hopefully, acceptance, parents need to do their best to make sure their child gets all the proper treatment and complies with this treatment. Compliant patients are in better health and live longer. They will also be the ones who survive to take advantage of new treatments as they are introduced. It is extremely important that both parents and patients understand this and comply fully with treatment. Some of the damage that iron does to the organs and glands is not reversible, so it is of utmost importance to be dedicated to chelation compliance from the beginning. Acceptance of the realities of thal treatment can give a patient the proper perspective to ensure compliance.
Thalassemics can live fairly normal lives. Thals go to school, travel, have careers, get married and have children. It is very important for parents to understand this, for not only do parents have to assure their child gets proper care, but they also need to recognize the tendency to be overprotective of their children. Thal children should be raised like all other children and given the same opportunities as anyone else. Please do not tell your children they can't do things because they will believe you. Encourage your kids. Give them direction. Help them achieve their goals but never tell them that they can't. Help them believe in themselves. You won't be doing any favors by being overprotective. When they become adults they need to be prepared like all other children. As a parent, you have to strike a balance between providing for their health and providing for their futures. This has been a major problem with thalassemics, as overprotective parents have not prepared their kids for the realities of life and how to live life as an independent adult. Thals are now living much longer and the thinking of parents needs to be adjusted to the fact that their children will become adults and have the same hopes and aspirations as any other person. Thalassemia involves many challenges but it can make better people of the parents. The dedication of the parents to the health of their children is the single most important factor as the child grows, but the parents have to remember that in addition to the physical health and development, the social and psychological health of the child must be taken into account.
The health issues of thalassemia majors are numerous and complex and are dealt with in depth in our discussion forums. The life of a major requires regular medical intervention in forms of treatment and monitoring, but this care has given thals a chance to have real lives. Your perspective and determination will have much to do with how well you and your children cope with thalassemia and the challenges it raises. If you make the conscious choice to deal with thalassemia through strength and the belief that your efforts are critical, your own perspective will become one ready to take on every new challenge. I ask all parents to educate themselves about thalassemia and to find the inner strength necessary to give your child every chance to have a real life. These comments are not just a pep talk. They are based on observation of many patients and their parents. When parents are conscious of the full needs of their children and their own role, the children will find themselves better prepared for adulthood.