Description, Causes and Risk Factors:
Alpha-thalassemia intermedia is an inherited blood disorder that affects a person's ability to produce hemoglobin, causing anemia. The disease is a form of alpha thalassemia and is very common in people from China, the Philippines, Thailand, Vietnam, Cambodia, Laos, and other Southeast Asian countries.
They are characterized by a reduction or complete absence of alpha-globin gene expression. Normal individuals have two alpha genes on each chromosome 16. The loss of one (-?) or both (--) of the cis-linked genes are the most common causes for alpha-thalassaemias intermedia. Patients with alpha-thalassaemia intermedia with only one functional alpha-globin gene (-?) develop chronic hemolytic anemia of variable severity. HbH (hemoglobin H) disease is the common cause alpha-thalassaemia intermedia. This condition is characterized by a strongly positive H-inclusion test. Non-deletional HbH disease has been described to be more severe than the deletional type 1. The most severe form of alpha-thalassaemia intermedia is Hb Bart's hydrops fetalis where there are no functional alpha-globin genes (--) and results in the condition where death occurs in utero or within a few hours of birth.
Patients with alpha thalassaemia-intermedia have moderate anaemia with Hb levels between 7-10 gm/dL. The manifestations include thalassaemia facies, jaundice and hepatosplenomegaly that range from mild-to-moderate. Growth and development is normal. Gallstones and iron overloading in the absence of blood transfusions have been seen. The H-inclusion test is strongly positive in these cases.
: According to researchers alpha-thalassaemia intermedia is caused by both deletion and non-deletion mutations in the alpha globin gene complex. In contrast to ?-thalassaemia, deletions are more common than non-deletional defects. Commonly, alpha-thalassaemia intermedia presents as HbH disease from the interaction of deletion of both the ?-globin genes in cis (?0
) (?-thal 1) and ?+
(?-thal 2) phenotype. The most common non-deletion single gene defect (?+
) is hemoglobin Constant Spring (HbCS). This is a termination codon defect results in a long mRNA with 31 extra amino acids being formed. The long mRNA is unstable resulting in reduced production of alpha-globin chains and a ?+
phenotype. HbH-Constant Spring has a more severe clinical phenotype than deletion HbH disease. The non-deletion molecular defect in the alpha-globin 1 gene CD59 results in the formation of hyperunstable alpha Hb variant. It is a rare cause for alpha-thalassaemia-intermedia when the mutation combines with a ?+
deletion defect. If the mutation occurs in the alpha2-globin gene it results in hydrops fetalis. mRNA formation in ?2:?1 is 3:1 and accounts for the condition being more severe when the ?2 gene is involved.
The true frequency of the molecular defect in the ?-globin 1 gene CD59 is unknown as the defect can only be ascertained by DNA studies. This alpha Hb variant is hyperunstable and has no product to be visualized by routine hematology studies. Screening for thalassaemia by blood counts and Hb subtyping will miss the diagnosis in contrast to beta-thalassaemia where determination of Hb subtypes presumptively identifies the presence of thalassaemia.
The most severe form of alpha thalassemia causes stillbirth (death of the unborn baby during birth or the late stages of pregnancy).
Other symptoms can include:
Bone deformities in the face.
- Growth failure.
- Shortness of breath.
- Yellow skin (jaundice).
Persons with the minor form of alpha and beta thalassemia have small red blood cells (which are identified by looking at their red blood cells under a microscope), but no symptoms.
Other complications may include:
- Cardiac abnormalities.
- Psychosocial problems.
- Vitamin deficiencies.
Diagnostic testing may include:
A series of blood tests and some related genetic studies can confirm whether a certain individual exhibits thalassemia or a carrier state. For a situation like both parents are said to be carriers, a consultation with a professional genetic counselor is highly recommended. This will assist a couple to whether to conceive or to undergo a fetus checked for thalassemia.
Blood tests that needs to be undertaken includes:
Complete blood count (CBC).Various blood cells such as red blood cells are measured through their size, amount, and maturity in a certain blood volume.
- Hemoglobin electrophoresis with A2 and F quantitation: This is a laboratory procedure that distinguishes the types of available hemoglobin (proteins from red blood cells) in the body.
FEP or free-erythrocyte protoporphyrin and serum ferritin:
FEP or free-erythrocyte protoporphyrin is a blood test that calibrates the non-complex, non-heme concentration of protoporphyrin in the blood. It is done to assess the blood for presence of too little amount of iron or too much amount of lead.
- Serum ferritin is tested to measure the ferritin amount present in the blood. This substance is the body's chief storage of iron protein. It is used to assess the iron in the body and examine the body's reaction to iron therapy. However, iron deficiency anemia is excluded during the result.
Prenatal diagnosis for alpha-thalassemia is available. The fetal status can be established through DNA studies preferably following CVS or placental biopsy near the end of the first trimester (eleven to thirteen weeks).
Genetic screening and counseling of parents is a pre-requisite, to determine the probabilities of the fetus being affected and the extent. Then the parents need to look at the permutations and what they would want to do in each possible eventuality.
As a general statement, both alpha-thalassemia trait (where individuals are healthy) and HbH disease (where there is chronic anemia but normal life expectancy) are compatible with continuing the pregnancy.
Alpha-thalassemia intermedia can cause severe anemia
if the person comes in contact with certain medications and chemicals. These medications and chemicals can lead to breakage of the red blood cells, and should be avoided by people with alpha-thalassemia intermedia. Severe anemia can also occur if the patient gets a high fever. Temperature should be closely monitored during illness and infections should be treated immediately to avoid high fevers. If you come into contact with any of the listed medications and/or chemicals, or if you experience high fever and/or any of the symptoms listed on the back, please contact your physician or health care provider immediately.
Alpha-thalassemia intermedia may cause mild-to-moderate hemolysis. Transfusions will occasionally be necessary depending upon the severity of the clinical condition. Transfusion-dependent patients develop iron overload because they have no physiologic process to remove excess iron from multiple transfusions. Therefore, they require treatment with an iron chelation starting between five and eight years of age.
Other treatment options may include: Bone marrow transplant.
NOTE: The above information is educational purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.