Alphathalassemia is particularly common among people of african, mediterranean, or southeast asian ancestry. Hypochromic microcytes and target cells are the main features in asymptomatic ind ividuals. Alphaglobin is expressed from four genes hba1 and hba2 on each chromosome 16 that are. Increased cardiothoracic ratio of the left twin of a pregnancy discordant for fetal homozygous.
Thalassemia is a type of thalassemia that is caused by a deficiency of the alpha globin protein. Thalassemia is a group of inherited blood disorders caused by defects in one or more genes responsible for producing the globin chains in hemoglobin. Alpha thalassemia is a blood disorder that reduces the production of normal hemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body. Patients with thalassemia minor or intermedia should be offered genetic counseling because offspring of. This lowers the amount of oxygen that cells receive, causing various health problems, including anemia. The hematologic features are very important for the selection of the appropriate molecular tests while determining the genotype. Two types of alphathalassemia can cause health problems.
Because alpha chains are shared by fetal and adult haemoglobin the disease is manifest in. Silent carriers of alpha thalassemia and persons with alpha or beta thalassemia trait are asymp tomatic and require no treatment. Thalassaemia disorders in humans caused by the deficiency of the alpha chain of hemoglobin have been well documented and validated throughout the world, by various stepwise diagnostic strategies and techniques. When there isnt enough hemoglobin, the bodys red blood cells dont function properly and they last shorter periods of time, so there are fewer healthy red blood cells traveling. Alphathalassemia pregnancies are rising in north america and require prenatal counseling, overall community education, and welldeveloped intrauterine management plans. The dna obtained from cultured amniotic fluid cells was studied. The alpha chain is involved in alpha thalassemia and the beta chain is affected in the more familiar beta thalassemia. Most carriers are defective in either one or two alpha globin genes out of four functional ones, with deletions being more common than point mutations. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. This is called the cis form of alpha thalassemia trait. Alpha thalassemia can occur in combination with hemoglobin s. The diagnosis of alphathalassaemia due to deletions is implemented by the electrophoretic analysis of genomic dna digested with restriction enzymes and hybridized with. Alphathalassemia is a blood disorder that reduces the bodys production of hemoglobin.
The ucsf fetal treatment center and ucsf benioff childrens hospitals have established the first multidisciplinary center for alpha thalassemia major. Hemoglobin h disease results from mutations of three aglobin genes. Clinically, these disorders cause a spectrum of disease that varies in severity depending on the nature of the mutations and the presence of various genetic modifiers. This signs and symptoms information for alpha thalassemia has been gathered from various sources, may not be fully accurate, and may not be the full list of alpha thalassemia signs or alpha thalassemia symptoms. Carriers of alphathalassemia do not need any treatment. If one parent has the cis form of alpha thalassemia trait, and the other parent is a silent carrier. Mutations in the genes that encode these proteins cause 2 major classes of thalassemia. There are four types of alpha thalassemia, hemoglobin bart hydrops fetalis syndrome or hb bart syndrome the more severe form, hbh disease, silent carrier state and trait. The woman had a first pregnancy terminated in the delivery of a hydropic fetus due to homozygous. Impaired 1, 2, 3, or 4 alpha globin chain productions can lead to a comparative excess of the beta globin chains. Furthermore, signs and symptoms of alpha thalassemia may vary on.
Laboratory diagnosis oflaboratory diagnosis of thalassemia dr. Is fairly common combination in populations of african descent. Diagnosis of alphathalassemia prenatal diagnosis of deletional alphathalassemia carrier screening for individuals from highrisk populations for alphathalassemia athal overview. When both parents have alpha thalassemia trait, there usually is a 25% or 1 in 4 chance in each pregnancy for the baby to have alpha.
Alphathalassemia is characterized by a deficit in the production of the. It is passed down from one or both parents through their genes. The couple requested prenatal diagnosis for the second pregnancy. Have less hb s present than those with sickle cell trait. Persons with the thalassemia trait have a normal life expectancy. Both of these genes provide instructions for making a protein called alphaglobin, which is a component subunit of hemoglobin people have two copies of the hba1 gene and two copies of the hba2 gene in each cell. People with hemoglobin h disease can have an enlarged spleen, low red blood cell. Prevention of thalassemia is based on public awareness of the disease, detection of carriers, genetic counselling, and prenatal testing. Red blood cell morpho logy is altered in patients with all forms of thalassemia.
Normal hemoglobin consists of two alpha chains and two beta chains. Alpha thalassemia, the heterozygous state with a single gene for alpha thalassemia, causes no symptoms or merely mild anemia because there is another gene still able to make alpha chains. Update on the diagnosis and management of thalassemia. Laboratory diagnosis of hemoglobinopathies and thalassemia. Thalassemia is a defect in alphachain synthesis in which one alpha trait, two. The flow chart shown in fig 4 summarizes the techniques for diagnosis of thalassemia and.
Inherited haemoglobin disorders, including thalassaemia and sicklecell disease, are the most common monogenic diseases worldwide. Laboratory diagnosis oflaboratory diagnosis of thalassemia. Diagnostic tests for alpha thalassemia including blood tests, urine tests, swabs, diagnostic tests, lab tests, and pathology testing. Each of the four alpha globin genes contributed to the. Alphathalassemia genetic and rare diseases information. When functional point mutations, frame shift mutations, nonsense mutations, and chain termination mutations occur within or around the coding sequences of the alphaglobin gene cluster hemoglobin is impaired. What if one parent has alpha thalassemia trait and the other parent is a silent carrier. The condition is caused by the disruption of one or more of the four resident homologous hemoglobin alpha genes.
Alpha and beta thalassemia american family physician. Prenatal diagnosis of alphathalassemia in a twin pregnancy. Pdf at present, thalassemia diseases are classified into. In betathalassemia, the beta globin genes are affected. Alpha thalassemia intermedia, or hemoglobin h disease, causes. Deletional forms result in a relatively mild anemia, whereas nondeletional. Alpha thalassemia typically results from deletions involving the hba1 and hba2 genes. Alpha thalassemia an overview sciencedirect topics. Laboratory diagnosis oflaboratory diagnosis of thalassemia yneed to start with patients individual history. Affected people have anemia, which can cause pale skin, weakness, fatigue, and more serious complications. Pdf clinical classification, screening and diagnosis for. Most cases of hemoglobin variants and alpha thalassemia are detected on the newborn screen, whereas beta thalassemia is not clinically apparent until about 46 months of life.
Alphathalassemia is a fairly common blood disorder that results in reduced amounts of hemoglobin, the protein in red blood cells that carries oxygen to cells in the body. Thalassemia standardofcare guidelines mobile optimized 3. Therefore, alpha thalassemia occurs when there is a disturbance in production of. In most cases, alpha thalassemia is diagnosed before a childs second birthday or through newborn screening, a blood test given when the child is first born. People with the second type of alpha thalassemia trait have 2 missing alpha globin genes on the same chromosome aa. Individuals with alpha thalassemia, particular the intermediate or severe forms, will benefit from referral to a thalassemia treatment center. Signs and symptoms of thalassemia in adults care whizz. The trans form of alpha thalassemia trait aa is common in africanamericans 2030 percent and people of african descent.
Its causes, risk factors, complications and what are the treatment options for thalassemia. Thalassemias involving delta, gamma, epsilon, and zeta chains are rare and usually not associated with significant disease outside of the neonatal period. This material may not otherwise be downloaded, copied, printed. The program is designed to address the complex diagnostic, prenatal, intrauterine, and perinatal management issues affecting a family with an alpha thalassemia major pregnancy. Not the preferred firsttier molecular test for carrier screening or diagnosis of alpha thalassemia. Pdf on mar 21, 2012, vefik arica and others published alpha thalassemia disorders find, read and cite all the. Betathalassemia is more common among people of mediterranean, middle eastern, southeast asian, or indian ancestry. The diagnosis of alpha thalassaemia due to deletions is implemented by the electrophoretic analysis of genomic dna digested with restriction enzymes and hybridized with. Know what are the signs and symptoms of thalassemia in adults. Thalassemia quantitative a quantitative decrease in the production of alpha or beta globin chain large deletions, point mutations, small insertiondeletion that leads to decreased transcription or an unstable transcript beta thalassemia results from mutations in beta genes pathogenesis a result of the free alpha subunits. The most severe form of alpha thalassemia, alpha thalassemia disease alpha thalassemia major can only happen when both parents have alpha thalassemia trait.
Any patient with an unexplained microcytic anemia should be referred to help establish a diagnosis. Thalassemias are a group of inherited microcytic, hemolytic anemias characterized by defective hemoglobin synthesis. Children with alpha thalassemia major may have a swollen abdomen or symptoms of anemia or failure to thrive. Alphathalassemia types, causes, diagnosis, treatment. Listed herein are the content contributors to the thalassemia standard of care guidelines. Diagnosis most persons with thalassemia trait are found inciden. Dna sequencing of hba1hba2 alpha globin 1 and alpha globin 2 is used to identify nondeletional alphathalassemia mutations when there is a strong clinical suspicion and athal alphaglobin gene analysis, is negative. Definitive diagnosis of thalassemia and hemoglobinopathies requires a comprehensive workup from complete blood count, hemoglobin analysis, and molecular studies to. Usually, patients with hemoglobin h disease are clinically well and survive without any. In alphathalassemia, at least one of the alpha globin genes has a mutation or aberration.
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