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.
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: 1 week; Refrigerated: 1 month; Frozen: 6 month

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 variants of a single alpha2 globin gene (-and is clinically asymptomatic (silent carrier). Alpha (0) thalassemia (trait) is caused by variants of both alpha2 globin
genes (-or variants in the alpha1 and alpha2 globin genes on the same chromosome, (--/and results in mild microcytic anemia. Hemoglobin H disease occurs due to variants
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 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.
Incidence:
Carrier frequency in Mediterranean (1:30-50), Middle Eastern, Southeast Asian (1:20), African, African-American (1:3).
Inheritance:
Autosomal recessive.
Cause:
Pathogenic variants in the alpha globin gene cluster.
Clinical Sensitivity:
99 percent.
Methodology:
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.
Limitations:
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. 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. 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 variants will not be detected. 

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

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

Note
Hotline History
N/A
CPT Codes

81259; 81269

Components
Component Test Code* Component Chart Name LOINC
2011709 HBA Seq, Del/Dup Specimen 31208-2
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.
Aliases
Alpha Globin (HBA1 and HBA2) Sequencing and Deletion/Duplication