Test Id : ATHAL

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.

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.

All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Specimen preferred to arrive within 96 hours of collection.

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

• Molecular Genetics: Congenital Inherited Diseases Patient Information
• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)

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.

Blood: 1 mL; Amniotic Fluid: 10 mL

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.

This test is for genetic deletions and duplications only.

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.

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.

An interpretive report will be provided.

An interpretive report will be provided.

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.

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

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.)

Monday, Wednesday

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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.

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)