Second-tier genetic test for detection of alpha thalassemia or alpha thalassemia trait. REQUIRES PERMISSION from ARUP's Genetic Counselor (800-242-2787, x2141) before ordering. Preferred initial screening test is deletion/duplication (2011622).
- Patient Preparation
- Contact ARUP's genetic counselor at (800) 242-2787 extension 2141 prior to test submission for collection requirements.
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Alpha thalassemia, caused by insufficient or absent alpha chain production, has a highly variable clinical presentation. Classic deletional alpha thalassemia is not detected by sequencing; deletional subtypes include:
Alpha thalassemia silent carrier: deletion of a single alpha globin gene (-a/aa); typically asymptomatic.
Alpha thalassemia trait: deletion of two alpha globin genes in trans (-a/-a), or cis (--/aa); mild microcytic anemia possible.
Hemoglobin H disease; deletion of three alpha globin genes (--/-a); hemolysis with Heinz bodies, moderate anemia, splenomegaly.
Hemoglobin Bart hydrops fetalis syndrome; deletion of four alpha globin genes (--/--); lethal in fetal or early neonatal period.
Non-deletional alpha globin mutations may be pathogenic or benign; both may result in an abnormal protein detectable by hemoglobin evaluation. Pathogenic non-deletional mutations often have a more severe effect than single gene deletions.
Incidence: Carrier frequency in Mediterranean (1:30-50), Middle Eastern, Southeast Asian (1:20), African, African-American (1:3).
Inheritance: Autosomal recessive.
Cause: Pathogenic HBA1 or HBA2 gene mutations.
Clinical Sensitivity: Up to 9 percent, depending on ethnicity. Most pathogenic HBA1 and/or HBA2 gene mutations are large deletions not detectable by sequencing.
Methodology: Bidirectional sequencing of the HBA1 and HBA2 coding regions, intron-exon boundaries, proximal promoter regions, 5' and 3' untranslated regions and polyadenylation signals.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Large deletions/duplications and some mutations of the regulatory regions, will not be detected. The phase of identified mutations may not be determined. Sequencing of both HBA1 and HBA2 may not be possible in individuals harboring large alpha globin deletions on both alleles. Rare syndromes associated with alpha thalassemia, such as ATR-X and ATR-16, will not be detected.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2001583||Alpha Globin (HBA) Sequencing Specimen||31208-2|
|2001585||Alpha Globin (HBA) Sequencing Interp|
- A globin sequencing
- Alpha Globin
- HBA1, HBA2 sequencing