- 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: High carrier frequency in Mediterranean (1 in 30 to 1 in 50), Middle Eastern, Southeast Asian (1 in 20), African and African-American (1 in 3) populations.
Inheritance: Autosomal recessive.
Cause: Pathogenic HBA1 or HBA2 gene mutations.
Clinical Sensitivity: Up to 10 percent for sequencing. Most pathogenic HBA1 and/or HBA2 gene mutations are large deletions not detectable by sequencing.
Methodology: Bidirectional sequencing of theHBA1 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. This test is not able to identify sequence variants in an alpha globin gene in cis with the common 3.7 kb deletion. Therefore, sequencing is not possible in individuals homozygous for the 3.7 kb deletion; individuals heterozygous for the 3.7 kb deletion will appear homozygous for sequence variants present on the non-deleted allele. Rare syndromes associated with alpha thalassemia, such as ATR-X and ATR-16, will not be detected.
See Compliance Statement C: www.aruplab.com/CS
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