Ordering Recommendation

Preferred first-tier genetic test for confirmation of suspected alpha thalassemia or alpha thalassemia trait. Detect common, rare, and novel deletions or duplications of the alpha globin gene cluster.

Mnemonic
HBA DD
Methodology

Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

Within 14 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (EDTA), pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

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

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable

Reference Interval

By report

Interpretive Data

Background Information: Alpha Globin (HBA1 and HBA2) Deletion/Duplication
Characteristics:
Alpha thalassemia is caused by decreased or absent synthesis of the hemoglobin alpha-chain resulting in variable clinical presentations. Alpha (+) thalassemia results from mutation of a single alpha2 globin gene (-a/aa) and is clinically asymptomatic (silent carrier). Alpha (0) thalassemia (trait) is caused by mutation of both alpha2 globin genes (-a/-a), or mutations in the alpha1 and alpha2 globin genes on the same chromosome, (--/aa) and results in mild microcytic anemia. Hemoglobin H disease occurs due to mutation of three alpha globin genes (--/-a) and results in hemolysis with Heinz bodies, moderate anemia, and splenomegaly. Hb Bart Hydrops Fetalis Syndrome results when mutations 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.
Incidence:
Carrier frequency in Mediterranean (1:30-50), Middle Eastern, Southeast Asian (1:20), African, African-American (1:3).
Inheritance:
Autosomal recessive.
Cause:
Pathogenic mutations in the alpha globin gene cluster.
Clinical Sensitivity:
Varies by ethnicity, up to 95 percent.
Methodology:
Multiplex ligation-dependent probe amplification (MLPA) of the alpha globin gene cluster (HBZ, HBM, HBA2, HBA1, HBQ1) and its HS-40 regulatory region.
Analytical Sensitivity and Specificity:
99 percent.
Limitations:
Diagnostic errors can occur due to rare sequence variations. Specific breakpoints of large deletions/duplications will not be determined; therefore, it may not be possible to distinguish mutations of similar size. This assay does not assess for non-deletional mutations within the coding or regulatory regions of the alpha globin cluster genes. 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 mutations will not be detected.

Compliance Category

Laboratory Developed Test (LDT)

Note
Hotline History
N/A
CPT Codes

81269

Components
Component Test Code* Component Chart Name LOINC
2011623 Alpha Globin (HBA1/2) DelDup Specimen 31208-2
2011624 Alpha Globin (HBA1/2) DelDup Interp 90040-7
* 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.
Aliases
  • A globin
  • Alpha globin gene analysis
  • Alpha globin mutations
  • Alpha thalassemia
Alpha Globin (HBA1 and HBA2) Deletion/Duplication (Temporary Delay as of 11/20/20 no referral available)