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Alpha thalassemia is a blood disorder that affects hemoglobin, a major component of red blood cells that carries oxygen in the body. Hemoglobin is a protein complex made up of two different chains. There are many forms of hemoglobin, but the primary type is made up of alpha chains and beta chains. Alpha thalassemia is caused by mutations involving the genes, HBA1 and HBA2, that code for the alpha chains.
Most individuals have two functional pairs or four functional copies of the alpha globin genes (one copy each of HBA1 and HBA2 on both chromosomes).
Carriers generally have either two or three functional alpha globin genes and do not have any symptoms.
Three functional alpha globin genes, silent carrier: These individuals are typically known as silent carriers, because they do not have any symptoms or abnormalities on a complete blood count. This status results from the presence of an alpha+ mutation (mutation that eliminates the function/presence of one copy of an alpha globin gene).
Two functional alpha globin genes, carrier: These carriers generally have mild anemia characterized by hypochromic (pale) and microcytic (small) red blood cells, which can be measured on a complete blood count. However, they usually do not have any symptoms of the disease (note exception below). Carrier status may result from the presence of two alpha+ mutations (eliminates function/presence of one copy of an alpha globin gene on each chromosome) or an alpha0 mutation (eliminates function/presence of both copies of the alpha globin genes on one chromosome).
Exception: There have been reports of individuals with two copies of certain types of point mutations who have a diagnosis of hemoglobin H disease with variable symptoms. One example of this is when individuals have two copies of the hemoglobin Constant Spring mutation, which is common in the Southeast Asian population.
Disease symptoms most typically occur if an individual has one or zero functional alpha globin genes.
One functional alpha globin gene, hemoglobin H disease: This form of alpha thalassemia is very variable. Disease severity ranges from asymptomatic to moderate microcytic/hypochromic anemia with the possibility of jaundice (yellowing of the skin or eyes), enlarged spleen, bone deformities, fatigue, and other minor complications.
Zero functional alpha globin genes, hemoglobin Bart syndrome: Individuals who have no functional copies or are missing all four copies of the associated genes almost always have this fatal form of alpha thalassemia. Hb Bart syndrome is generally associated with death in utero due to the buildup of excess fluid in the body and tissues (hydrops fetalis). Signs and symptoms in the newborn period can include severe anemia, hepatosplenomegaly (enlarged liver and spleen), and birth defects of the heart, urinary system, and genitalia. Most babies with this condition are stillborn or die soon after birth.
The carrier frequency and incidence of alpha thalassemia vary by the type and population. Carrier frequency of this condition is reported to be the highest in individuals of Southeast Asian, African, West Indian, and Mediterranean descent. In 2010, the estimated number of worldwide annual births of patients with Hb H disease was 9,568 and with Hb Bart syndrome was 5,183. Therefore, the worldwide birth prevalence of Hb H disease and Hb Bart's hydrops is estimated at ~1/14500 and ~1/27000, respectively; however, for Hb Bart's hydrops, this is likely to be an underestimate because most at-risk couples are not currently identified.
Alpha thalassemia carrier status does not necessitate treatment. Treatment for hemoglobin H disease varies based on the severity of the symptoms. For many individuals, blood transfusions are given during crises, which are episodic and usually precipitated by environmental stressors, like oxidant medications or fever. Individuals with more severe symptoms may require regular blood transfusions, folic acid supplementation, prophylactic antibiotics, iron chelation therapy (removal of excess iron from the body), and possible hemoglobin F-enhancing agents and splenectomy.
Extremely rare cases of survivors with hemoglobin Bart syndrome have been reported when fetal blood transfusions were given, followed by regular treatments similar to those who have hemoglobin H disease. Treatments or surgical correction of potential birth defects may also be available. However, there is a high risk for intellectual and physical disability in these rare survivors. These individuals may be candidates for hematopoietic stem cell transplantation.
Because hemoglobin H disease can be variable, prognosis ultimately depends on the severity of the disease. Mild disease may be manageable with little effect on daily life. However, more severe disease will necessitate frequent and regular therapy, and may be associated with a shortened lifespan. Untreated, the prognosis is poor with a shortened lifespan of up to age 5 years. However, when treated, individuals with hemoglobin H disease have a lifespan that approaches normal.
Hemoglobin Bart syndrome is the most severe clinical condition related to alpha thalassemia, and death may occur in utero or in the newborn period. Of note, there may also be maternal complications during pregnancy if the fetus has hemoglobin Bart syndrome. These complications include preeclampsia (high blood pressure, fluid build-up/swelling, protein in the urine), polyhydramnios (excessive amniotic fluid) or oligohydramnios (reduced amniotic fluid), hemorrhage, and premature delivery.
The Cooley's Anemia Foundation is dedicated to serving people afflicted with various forms of thalassemia.
330 Seventh Ave, #200, New York, NY 10001
The Genetics Home Reference is a guide to understanding genetic conditions.
Reference and Web Services National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894
The March of Dimes researches the problems that threaten the health of babies.
March of Dimes National Office, 1275 Mamaroneck Avenue, White Plains, NY 10605