Comprehensive genetic test for detection of alpha thalassemia or alpha thalassemia trait.
- 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
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2011709||HBA Seq, Del/Dup Specimen||31208-2|
|2011710||HBA Seq, Del/Dup Interp||35474-6|