Test ID: WASEQ    
Alpha Globin Gene Sequencing, Varies

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

A hemoglobin electrophoresis evaluation (HBELC / Hemoglobin Electrophoresis Cascade, 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.

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 variants 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 (Hb CS).

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.

An interpretive report will be provided.

An interpretive report will be provided.

This assay will not detect large deletions or duplications within the alpha globin genes. Therefore, test results should be interpreted in the context of hemoglobin electrophoresis, clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

Rare genetic alterations 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.

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 Clinical Laboratory Medicine. Second edition. Edited by KD McMlatchey. Philadelphia, Lippincott Williams and Wilkins. 2002, pp 866-895

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