Alpha-thalassemia

The severity of the symptoms of alpha-thalassemia varies from person to person. Symptoms usually start within the first year of life. Over time symptoms such as fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead, may worsen and indicate the need for a blood transfusion. The ages at which these symptoms worsen, if at all, depends on the severity of disease in each individual.

Those with alpha-thalassemia will show symptoms. However, the severity of the symptoms will vary from person to person and according to the specific form of the disease. Mutations in the HBA1 and HBA2 genes lead to changes in the hemoglobin protein; however, it is the quantity of the altered genes (mutations) that determine the presence and severity of symptoms of alpha-thalassemia.

There are four types of alpha-thalassemia. These include hemoglobin Bart (Hb Bart) disease, hemoglobin H (HbH) disease, alpha-thalassemia trait and alpha-thalassemia silent carriers. The symptoms of alpha-thalassemia are variable, according to the severity of disease. Alpha-thalassemia is caused by mutations in the HBA1 and/or HBA2 genes. We each have two copies of HBA1 and HBA2, for a total of four copies.

Those who have no working copies or HBA1 or HBA2 have the most severe form, hemoglobin Bart syndrome. Symptoms begin prenatally and include swelling of the body, fluid surrounding the brain, heart and lungs, severe anemia, enlarged liver and spleen, heart defects and defects of the urinary and genital system. Death usually occurs in newborns. These pregnancies can be complicated by preeclampia (extreme hypertension), excessive amniotic fluid or reduced amniotic fluid, bleeding in the genital tract, and premature delivery.

The less severe form of alpha-thalassemia is called hemoglobin H disease. These individuals have one working copy of HBA1 or HBA2. Symptoms of this form vary from mild to more severe. Symptoms usually start by age one, but for some, symptoms do not begin until adulthood. Those with more severe symptoms can have anemia, enlarged spleen, gallstones, slowed growth and decreased bone density. 24% to 80% of these patients receive blood transfusions, and blood transfusions start between 0 and 3 years of age. Those with less severe symptoms are less like to receive blood transfusions, with 3% to 29% chance. The age at first blood transfusion is older, between 6 and 15 years of age. The anemia, enlarged spleen, gallstones, slowed growth and decreased bone density are more mild. Those with hemoglobin H disease may experience bone changes of the face, such as enlargement of the upper jaw, protruding of the forehead and enlargement of the cheekbones. In very severe cases, infants have died prenatally or soon after birth. The cause of this extreme variability is unknown.

Those with alpha-thalassemia trait have two working copies of HBA1 or HBA2. They have mild anemia. Silent carriers have three working copies or HBA1 or HBA2 and do not experience symptoms.

During pregnancy, women with hemoglobin H may experience more severe anemia. In the third trimester, increased rate of premature labor, preeclampsia and congestive heart failure have been reported.

There are four different types of alpha-thalassemia. These include hemoglobin Bart (Hb Bart) disease, hemoglobin H (HbH) disease, alpha-thalassemia trait and alpha-thalassemia silent carriers. Each type includes a range of symptoms.

The symptoms of alpha-thalassemia are variable, according to the severity of disease. Alpha-thalassemia is caused by mutations in the HBA1 and/or HBA2 genes. We each have two copies of HBA1 and HBA2, for a total of four copies.

Those who have no working copies of HBA1 or HBA2 have the most severe form, hemoglobin Bart syndrome. Symptoms begin prenatally and death usually occurs in newborns. Doctors should be aware that these pregnancies can be complicated by preeclampia (extreme hypertension), excessive amniotic fluid or reduced amniotic fluid, bleeding in the genital tract, and premature delivery. During pregnancy women with alpha-thalassemia may experience more severe anemia. In the third trimester, increased rate of premature labor, preeclampsia and congestive heart failure have been reported.

The less severe form of alpha-thalassemia is called hemoglobin H disease. These individuals have one working copy of HBA1 or HBA2. Symptoms of this form vary from mild to more severe. Symptoms usually start by age one, but for some symptoms do not begin until adulthood. Doctors should watch for anemia, enlarged spleen, gallstones, slowed growth and decreased bone density. With time, patients may benefit from a blood transfusion. Indications that a blood transfusion may increase quality of life include fatigue, anemia, poor growth, poor weight gain and bone changes, such as enlargement of the upper jaw, around the eyes and forehead.

Those with alpha-thalassemia trait have two working copies of HBA1 or HBA2. They should be watched for mild anemia.

Alpha-thalassemia can look like several other conditions described below.

The most severe form of alpha-thalassemia, hemoglobin Bart, results in a condition called hydrops fetalis, an accumulation of fluid in the fetus. Hydrops fetalis can occur as a result of many other conditions, including immune-related disorders, fetal heart abnormalities, chromosome abnormalities, fetal infections, genetic disorders, and maternal and placental disorders. A high level of a form of hemoglobin, called hemoglobin Barts, can distinguish alpha-thalassemia from these other conditions.

Alpha-thalassemia is associated with hemolytic anemia, a condition in which blood cells are prematurely destroyed, causing anemia. There are other conditions associated with hemolytic anemia, including hereditary spherocytosis/elliptocysosis and G6PD deficiency. Blood tests can distinguish these.

Alpha-thalassemia is associated with anemia. There are many causes of anemia. These include iron deficiency, B12 deficiency, and folate deficiency. Sideroblastic anemia is caused by the production of abnormal red blood cells.

A syndrome called alpha-thalassemia X-linked intellectual disability (ATRX) syndrome involves alpha-thalassemia. However, these individuals also have other symptoms, including distinct facial features, genital abnormalities, and severe developmental delay.

A similar blood condition is called beta-thalassemia. This disease also involves abnormal hemoglobin and symptoms including anemia, enlarged liver and spleen, delayed growth and the need for blood transfusions. Blood studies can distinguish between alpha and beta thalassemia. Other abnormalities of hemoglobin can look similar to alpha-thalassemia.

Lead poisoning can cause red blood cells to look smaller, similar to the red blood cells of those with alpha-thalassemia.

Blood cancers, such as leukemia, lymphoma and multiple myeloma can mimic alpha-thalassemia.

This disease has a range of symptoms, from mild to very severe; however, the symptom that all individuals with this condition share is anemia. Anemia typically causes pale skin, weakness, and fatigue. People with the mild form of the disease may be misdiagnosed as having low iron levels but when given iron, their symptoms will not improve, indicating the need for further investigation.