Interpretive Handbook

Test 9499 :
Alpha-Globin Gene Analysis

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The thalassemias are a group of inherited conditions characterized by decreased synthesis of 1 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 mutations. 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 Bart, with hydrops fetalis and almost invariably in utero demise


Less frequently alpha-thalassemia results from single point mutations. The most common nondeletion mutation is Hemoglobin Constant Spring (HbCS) (HBA2: c.427T >C). Point mutations other than HbCS and alpha-thalassemia Saudi are not detected by this assay.


Alpha-thalassemia occurs in all ethnic groups but is especially common 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 point mutations) forms of alpha-thalassemia are found in individuals with Mediterranean ancestry. Deletions in cis (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 the fatal hemoglobin Bart hydrops fetalis syndrome.

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis of alpha-thalassemia


Prenatal diagnosis of deletional alpha-thalassemia


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


Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 may detect other diseases or conditions for which this test was not specifically intended. Results of the 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 polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.


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


This assay cannot be performed on chorionic villus specimens.


Hemoglobin Constant Spring and alpha-thalassemia Saudi are the only nondeletion types of alpha-thalassemia that will be detected by this assay. This test is not useful for diagnosis or confirmation of beta-thalassemia or hemoglobinopathies.


Hemoglobin electrophoresis should usually be done prior to this test to exclude other diagnoses or to identify non deletion types of alpha-thalassemia.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Harteveld CL, Voskamp A, Phylipsen M, et al: Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterized by high resolution multiplex ligation-dependent probe amplification. J Med Genet 2005; 42:922-931

2. Harteveld CL, Higgs DR: Alpha-thalassemia. Orphanet J Rare Dis 2010;5:13