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HelpTest Code ATHAL Alpha-Globin Gene Analysis, Varies
Reporting Name
Alpha-Globin Gene AnalysisUseful For
Diagnosis of alpha-thalassemia
Prenatal diagnosis of deletional alpha-thalassemia
Carrier screening for individuals from high-risk populations for alpha-thalassemia
This test is not useful for diagnosis or confirmation of beta-thalassemia or hemoglobinopathies.
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| ATHL | Alpha-Globin Gene Analysis (ATHL) | No | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULAF | Amniotic Fluid Culture/Genetic Test | Yes | No |
| MATCC | Maternal Cell Contamination, B | Yes | No |
Testing Algorithm
For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added at an additional charge.
For any prenatal specimen that is received, maternal cell contamination studies will be added.
Method Name
Dosage Analysis by Polymerase Chain Reaction (PCR)/Multiplex Ligation-Dependent Probe Amplification (MLPA)/Luminex Technology
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
VariesOrdering Guidance
This assay cannot be performed on chorionic villus specimens.
Point alterations are not detected by this assay. For detection of single point and other nondeletion variants, order WASEQ / Alpha Globin Gene Sequencing, Varies if clinically indicated.
Additional Testing Requirements
All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated
Prenatal Specimens
Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.
Specimen Type: Amniotic fluid
Container/Tube: Amniotic fluid container
Specimen Volume: 20 mL
Specimen Stability Information: Refrigerated (preferred)/Ambient
Acceptable:
Specimen Type: Confluent cultured cells
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured cells from another laboratory.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Specimen Minimum Volume
Blood: 1 mL; Amniotic Fluid: 10 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Special Instructions
Reference Values
An interpretive report will be provided.
Day(s) Performed
Monday, Wednesday
CPT Code Information
81269
88235-Tissue culture for amniotic fluid (if appropriate)
88240-Cryopreservation (if appropriate)
81265-Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| ATHAL | Alpha-Globin Gene Analysis | 90040-7 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 52834 | Result Summary | 50397-9 |
| 52835 | Result | 82939-0 |
| 52836 | Interpretation | 69047-9 |
| 54871 | Additional Information | 48767-8 |
| 52837 | Specimen | 31208-2 |
| 52838 | Source | 31208-2 |
| 52839 | Method | 85069-3 |
| 52840 | Released By | 18771-6 |
Clinical Information
The thalassemias are a group of inherited conditions characterized by decreased synthesis of one or more of the globin chains, resulting in an imbalance in the relative amounts of the alpha and beta chains. The excess normal chains precipitate in the cell, damaging the membrane and leading to premature red blood cell destruction. Additionally, the defect in hemoglobin synthesis produces a hypochromic, microcytic anemia. The frequency of thalassemia is due to the protective advantage against malaria that it gives carriers. Consequently, thalassemias are prevalent in populations from equatorial regions in the world where malaria is endemic.
Alpha-thalassemia is caused by decreased synthesis of alpha-globin chains. Four alpha-globin genes are normally present (2 on each chromosome 16). One, 2, 3, or 4 alpha-globin genes may be deleted or, less commonly, contain variants. Deletions account for approximately 90% of disease-causing alleles in alpha thalassemia. Phenotypically, these deletions result in 4 categories of disease expression:
-Deletion of 1 alpha-chain: Silent carrier state, with a normal phenotype
-Deletion of 2 alpha-chains: Alpha-thalassemia trait (alpha-1 thalassemia), with mild hematologic changes but no major clinical difficulties
-Deletion of 3 alpha-chains: Hemoglobin H disease, which is extremely variable but usually includes anemia due to hemolysis, jaundice, and hepatosplenomegaly
-Deletion of all 4 alpha-chains: Hemoglobin Bart, with hydrops fetalis and almost invariably in utero demise
Less frequently, alpha-thalassemia results from single point alterations, such as hemoglobin Constant Spring  (HBA2: c.427T >C). Note: these point alterations are not detected by this assay.
Alpha-thalassemia occurs in all ethnic groups but is especially common in individuals of Southeast Asian and African ancestry. It is also frequent in individuals of Mediterranean ancestry. The carrier frequency is estimated to be 1 in 20 for Southeast Asians, 1 in 30 for African Americans, and 1 in 30 to 1 in 50 for individuals of Mediterranean ancestry. Both deletional and nondeletional (caused by point alterations) forms of alpha-thalassemia are found in individuals with Mediterranean ancestry. Deletions in cis (deletions on the same chromosome) are rare in African or Mediterranean populations but are prevalent in Asian populations. Couples in which both partners carry deletions in cis are at risk of having a child with the fatal hemoglobin Bart hydrops fetalis syndrome.
Interpretation
An interpretive report will be provided.
Cautions
Hemoglobin electrophoresis should usually be done prior to this test to exclude other diagnoses or to identify nondeletion types of alpha-thalassemia.
In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.
Rare alterations (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If the results obtained do not match the clinical findings, additional testing should be considered.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.
Clinical Reference
1. Harteveld CL, Voskamp A, Phylipsen M, et al: Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterized by high resolution multiplex ligation-dependent probe amplification. J Med Genet. 2005 Dec;42(12):922-931. doi: 10.1136/jmg.2005.033597
2. Harteveld CL, Higgs DR: Alpha-thalassemia. Orphanet J Rare Dis. 2010 May;5:13. doi: 10.1186/1750-1172-5-13
3. Bunn HF, Forget BG: Hemoglobin: Molecular, Genetic and Clinical Aspects. 2nd ed. WB Saunders Company; 1986
4. Weatherall DJ, Higgs DR, Clegg JB, Hill AS, Nicholls R: Heterogeneity and origins of the alpha-thalassemias. Birth Defects Origi Artic Ser. 1987;23(5A):3-14
Method Description
This test is a direct variant analysis assay. Deletions and duplications within the alpha-globin locus are identified by a multiplex ligation-dependent probe amplification assay. Fifteen probes that hybridize throughout the alpha-globin locus from the HS40 promoter region through the 3'HVR region are utilized in order to maximize the information needed to map the approximate location of nearly all DNA deletions that occur. In addition, a polymerase chain reaction-based assay is used to detect the presence of the alpha-3.7 and alpha-4.2 deletions.(Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002 Jun 15;30[12]:e57. doi: 10.1093/nar/gnf056.)
Report Available
9 to 13 daysSpecimen Retention Time
Whole Blood: 2 weeks (if available); Extracted DNA: 3 monthsTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521)
3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755) with the specimen.