Ordering Recommendation

Comprehensive genetic test to detect alpha thalassemia or alpha thalassemia trait.

New York DOH Approval Status

This test is New York state approved.

Specimen Required

Patient Preparation

Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature


Unacceptable Conditions

Frozen specimens


Ambient: 1 week; Refrigerated: 1 month; Frozen: unacceptable


Multiplex Ligation-Dependent Probe Amplification (MLPA)/Sequencing/Polymerase Chain Reaction (PCR)




14-21 days

Reference Interval

Interpretive Data

Background Information for Alpha Globin (HBA1 and HBA2) Sequencing and Deletion/Duplication
Alpha thalassemia is caused by decreased or absent synthesis of the hemoglobin alpha chain resulting in variable clinical presentations. Alpha (+) thalassemia results from variants of a single HBA2 globin gene (-a/aa) and is clinically asymptomatic (silent carrier). Alpha (0) thalassemia (trait) is caused by variants of both HBA2 globin
genes (-a/-a) or variants in the HBA1 and HBA2 globin genes on the same chromosome (--/aa) and results in mild microcytic anemia. Hemoglobin H disease occurs due to variants of three alpha globin genes (--/-a) and results in hemolysis with Heinz bodies, moderate anemia, and splenomegaly. Hb Bart hydrops fetalis syndrome results when variants occur in all four alpha globin genes (--/--) and is lethal in the fetal or early neonatal period. Alpha globin gene triplications result in three active alpha globin genes on a single chromosome. Nondeletional alpha globin variants may be pathogenic or benign; both may result in an abnormal protein detectable by hemoglobin evaluation. Pathogenic nondeletional variants often have a more severe effect than single gene deletions.
Carrier frequency in Mediterranean (1:30-50), Middle Eastern, Southeast Asian (1:20), African, African American (1:3).
Autosomal recessive.
Pathogenic variants in the alpha globin gene cluster.
Clinical Sensitivity:
99 percent.
Bidirectional sequencing of the HBA1 and HBA2 coding regions, intron-exon boundaries and 3' polyadenylation signal. Multiplex ligation-dependent probe amplification (MLPA) of the alpha globin gene cluster (HBZ, HBM, HBA1, HBA2, HBQ1) and its HS-40 regulatory region.
Analytical Sensitivity and Specificity:
99 percent.
Diagnostic errors can occur due to rare sequence variations. Sequence analysis will not detect all regulatory region variants or variants in alpha globin cluster genes other than HBA1 and HBA2. Sequencing of both HBA1 and HBA2 may not be possible in individuals harboring large alpha globin deletions on both alleles. This assay is unable to sequence HBA2-HBA1 fusion genes; thus, HBA1 or HBA2 sequence variants occurring in cis with a 3.7 kb deletion or other HBA2-HBA1 hybrid gene will not be detected (e.g., Hb G -Philadelphia will not be detected when in cis with the 3.7 kb deletion). It may not be possible to determine phase of identified sequence variants. Specific breakpoints of large deletions/duplications will not be determined; therefore, it may not be possible to distinguish variants of similar size. Individuals carrying both a deletion and duplication within the alpha globin gene cluster may appear to have a normal number of alpha globin gene copies. Rare syndromic or acquired forms of alpha thalassemia associated with ATRX variants will not be detected.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Compliance Category

Laboratory Developed Test (LDT)


Hotline History


CPT Codes

81259; 81269


Component Test Code* Component Chart Name LOINC
2011709 HBA Seq, Del/Dup Specimen 66746-9
2011710 HBA Seq, Del/Dup Interp 35474-6
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.


Alpha Globin (HBA1 and HBA2) Sequencing and Deletion/Duplication