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Alpha Globin (HBA1 and HBA2) Sequencing and Deletion/Duplication
2011708
Ordering Recommendation

Comprehensive genetic test for detection of alpha thalassemia or alpha thalassemia trait.

Mnemonic
HBA FGA
Methodology
Polymerase Chain Reaction/Sequencing./Multiplex Ligation-dependent Probe Amplification.
Performed
Sun- Sat
Reported
14-21 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
ARUP Consult®
Disease Topics
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
Interpretive Data
Background Information for Alpha Globin (HBA1 and HBA2) Sequencing and 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 (-/) and is clinically asymptomatic (silent carrier). Alpha (0) thalassemia (trait) is caused by mutation of both alpha2 globin
genes (-/-), or mutations in the alpha1 and alpha2 globin genes on the same chromosome, (--/) and results in mild microcytic anemia. Hemoglobin H disease occurs due to mutation
of three alpha globin genes (--/-) 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.
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 mutations in the alpha globin gene cluster.
Clinical Sensitivity: 99 percent.
Methodology: Bidirectional sequencing of the HBA1 and HBA2 coding regions, intron-exon boundaries, proximal promoter regions, 5' and 3' untranslated regions, and polyadenylation
signals. 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.
Limitations: Diagnostic errors can occur due to rare sequence variations. Sequence analysis will not detect all regulatory region mutations or mutations in alpha globin cluster genes other than HBA1 and HBA2. 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 mutations 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. Sequencing of both HBA1 and HBA2 may not be possible in individuals harboring large alpha globin deletions on both alleles. Rare syndromic or acquired forms of alpha thalassemia associated with ATRX mutations will not be detected.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Components
Component Test Code*Component Chart NameLOINC
2011709HBA Seq, Del/Dup Specimen31208-2
2011710HBA Seq, Del/Dup Interp35474-6
* 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.
Aliases