Test Catalog

Test ID: WASEQ    
Alpha Globin Gene Sequencing, Varies

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

Diagnosing nondeletional alpha thalassemia


Testing for nondeletional alpha thalassemia in a symptomatic individual


Follow-up testing to an abnormal hemoglobin electrophoresis that identified an alpha-globin chain variant

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

A hemoglobin electrophoresis evaluation (HBEL1 / Hemoglobin Electrophoresis Evaluation, Blood) is always indicated prior to alpha globin gene sequencing because these conditions can be complex and protein data allows accurate and rapid classification of the patient phenotype.


Not the preferred first-tier molecular test for carrier screening or diagnosis of alpha thalassemia. This test is used to identify nondeletional alpha-thalassemia variants when there is a strong clinical suspicion and ATHAL / Alpha-Globin Gene Analysis, Varies, is negative. This test can also identify alpha globin variants that can result in variable phenotypes, such as erythrocytosis, chronic hemolytic anemia, and many that are clinically benign.

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

Alpha globin gene sequencing detects alpha globin variants and nondeletional alpha thalassemia variants.


Alpha thalassemia is the most common monogenic condition in the world. It is estimated that up to 5% of the world's population carries at least 1 alpha thalassemia variant and, in the United States, approximately 30% of African Americans are thought to carry an alpha thalassemia variant. Alpha thalassemia variations are most common in individuals of Southeastern Asian, African, Mediterranean, Indian, and Middle Eastern descent, but they can be found in persons from any ethnic group.


Four alpha-globin genes are normally present, 2 copies on each chromosome 16. Alpha thalassemia variants result in decreased alpha-globin chain production. In general, alpha thalassemia is characterized by hypochromic, microcytic anemia and varies clinically from asymptomatic (alpha thalassemia silent carrier and alpha thalassemia trait) to lethal hemolytic anemia (hemoglobin: Hb Barts hydrops fetalis).


Large deletions of the alpha globin genes account for approximately 90% of alpha thalassemia alterations, and these variations will not be detected by alpha-globin gene sequencing. Other variants, such as point alterations or small deletions within the alpha-globin genes, account for most of the remaining 10% of alpha thalassemia variations. These nondeletional subtypes can be detected by alpha globin gene sequencing. The most common nondeletional alpha thalassemia variant is Hb Constant Spring (HbCS).


The majority of alpha globin chain variants are clinically and hematologically benign however, some cause erythrocytosis and chronic hemolytic anemia. Hemoglobin electrophoresis may not be able to confirm their identity. In these instances, alpha-globin gene sequencing can be useful.

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.

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

Clinical Reference Recommendations for in-depth reading of a clinical nature

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

2. Hoyer JD, Hoffman DR: The Thalassemia and hemoglobinopathy syndromes. In: McClatchey, KD, ed. Clinical Laboratory Medicine. 2nd ed. Lippincott Williams and Wilkins. 2002;866-895

3. Farashi S, Harteveld CL: Molecular basis of a-thalassemia. Blood Cells Mol Dis. 2018 May;70:43-53. doi: 10.1016/j.bcmd.2017.09.004

4. Henderson SJ, Timbs AT, McCarthy J, et al: Ten years of routine a- and B-globin gene sequencing in UK hemoglobinopathy referrals reveals 60 novel mutations. Hemoglobin. 2016;40(2):75-84. doi: 10.3109/03630269.2015.1113990

Special Instructions Library of PDFs including pertinent information and forms related to the test