26643 Alpha Globin Cluster Locus Deletion/Duplication, Varies (AGDD)

​AGDD; AGPB; Alpha Globin; Alpha Thalassemia; Alpha-Thalassemia; ATHAL; HBA1; HBA2; Hemoglobin Bart; Hemoglobin-H Disease; Hydrops Fetalis; Thalassemia, Alpha; ABC​​​​

​​Diagnosis of alpha-thalassemia

Prenatal diagnosis of deletional alpha-thalassemia

Carrier screening for individuals from high-risk populations for alpha-thalassemia

This test is not useful for diagnosis or confirmation of beta-thalassemia or hemoglobinopathies.

This test is for genetic deletions and duplications only. 

Sequence variants, other than the alpha T-Saudi and hemoglobin constant spring alterations, are not detected by this assay.

​Invert several times to mix blood.

Send whole blood specimen in original tube. Do not aliquot.

​Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.  ​

Specimen preferred to arrive within 96 hours of collection. ​

​All specimens will be evaluated at Mayo Clinic Laboratories for test suitability. 

​​Hemoglobin electrophoresis should usually be done prior to this test to exclude other diagnoses.

In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. ​In certain circumstances, these control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

Rare alterations (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If the results obtained do not match the clinical findings, additional testing should be considered. 

Test results should be interpreted in the context of clinical findings, family history,​ and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete. ​

​The thalassemias are a group of inherited conditions characterized by decreased synthesis of one or more of the globin chains, resulting in an imbalance in the relative amounts of the alpha and beta chains. The excess normal chains precipitate in the cell, damaging the membrane and leading to premature red blood cell destruction. Additionally, the defect in hemoglobin synthesis produces a hypochromic, microcytic anemia. The frequency of thalassemia is due to the protective advantage against malaria that it gives carriers. Consequently, thalassemias are prevalent in populations from equatorial regions in the world where malaria is endemic.

Alpha-thalassemia is caused by decreased synthesis of alpha-globin chains. Four alpha-globin genes are normally present (2 on each chromosome 16). One, 2, 3, or 4 alpha-globin genes may be deleted or, less commonly, contain variants. Deletions account for approximately 90% of disease-causing alleles in alpha thalassemia. Phenotypically, these deletions result in 4 categories of disease expression:
-Deletion of 1 alpha-chain: Silent carrier state, with a normal phenotype
-Deletion of 2 alpha-chains: Alpha-thalassemia trait (alpha-1 thalassemia), with mild hematologic changes but no major clinical difficulties
-Deletion of 3 alpha-chains: Hemoglobin H disease, which is extremely variable but usually includes anemia due to hemolysis, jaundice, and hepatosplenomegaly
-Deletion of all 4 alpha-chains: Hemoglobin Barts hydrops fetalis, and almost invariably in utero fetal demise or early after birth, if left untreated. Samples with protein effects of intrauterine transfusion are increasingly common.

Less frequently, alpha-thalassemia results from single point alterations, such as hemoglobin Constant Spring (HBA2: c.427T >C).

Alpha-thalassemia occurs in all ancestral groups but is especially common in individuals of Southeast Asian and African ancestry. It is also frequent in individuals of Mediterranean ancestry. The carrier frequency is estimated to be 1 in 20 for Southeast Asians, 1 in 30 for African Americans, and 1 in 30 to 1 in 50 for individuals of Mediterranean ancestry. Both deletional and nondeletional (caused by sequence alterations) forms of alpha-thalassemia are found in individuals with Mediterranean ancestry. Those of Arab ancestry can carry a fairly common sequence alteration, called alpha- T-Saudi. Deletions in cis (two deletions on the same chromosome) are rare in African or Mediterranean populations but are prevalent in Asian populations. Couples in which both partners carry deletions in cis are at risk of having a child with hemoglobin H disease or hemoglobin Bart hydrops fetalis syndrome.