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Test Code NHHA Hereditary Hemolytic Anemia Gene Panel, Next-Generation Sequencing, Varies


Ordering Guidance


Multiple hematology gene panels are available. For more information see NHHA and Subpanel Comparison Gene List.

 

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.



Additional Testing Requirements


This test is best interpreted in the context of protein studies and peripheral blood findings. Prior to sending this test, Coombs testing should be negative, laboratory testing should indicate a hemolytic process, and consider evaluating a peripheral blood smear. In addition, protein analysis for hereditary causes of hemolytic anemia can be provided by ordering HAEV1 / Hemolytic Anemia Evaluation Profile, Blood. Fill out the information sheet and indicate that a next-generation sequencing test was also ordered. Additionally, providing complete blood cell count data and clinical notes will allow a more precise interpretation of results.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


1. Metabolic Hematology Next-Generation Sequencing (NGS) Patient Information is required. Testing may proceed without the patient information; however, the information aids in providing a more thorough interpretation. Ordering providers are strongly encouraged to fill out the form and send with the specimen.

2. If form not provided, include the following information with the test request: clinical diagnosis, pertinent clinical history (ie, complete blood cell count results and relevant clinical notes), and differentials based on previous enzyme testing, clinical or morphologic presentation.



Specimen Required


Specimen Type: Whole blood

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD)

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


Forms

1. Metabolic Hematology Next-Generation Sequencing (NGS) Patient Information (T816) is required.

2. 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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755)with the specimen.

Secondary ID

619033

Useful For

Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of hereditary hemolytic anemias, including red blood cell (RBC) membrane/hydration disorders, RBC enzymopathies, and congenital dyserythropoietic anemia

 

Comprehensive testing for patients in whom previous targeted gene variant analyses were negative for a specific hereditary hemolytic anemia

 

Establishing a diagnosis of a hereditary hemolytic anemia or related disorder, allowing for appropriate management and surveillance of disease features based on the gene involved, especially if splenectomy is a consideration(2)

 

Identifying variants within genes associated with phenotypic severity, allowing for predictive testing and further genetic counseling

Genetics Test Information

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 37 genes associated with hereditary hemolytic anemia: ABCB6, AHSP, AK1, ALDOA, ANK1, BCL11A, CDIN1 (C15orf41), CD59, CDAN1, EPB41, EPB42, G6PD, GATA1, GCLC, GPI, GSR, GSS, GYPC, HK1, HMOX1, KCNN4, KIF23, KLF1, NT5C3A, PFKM, PGK1, PGLS, PIEZO1, PKLR, RHAG, SEC23B, SLC2A1, SLC4A1, SPTA1, SPTB, TMPRSS6, and TPI1. See Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for hereditary hemolytic anemia.

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

Hereditary Hemolytic Anemia, NGS

Specimen Type

Varies

Specimen Minimum Volume

1 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.

Clinical Information

Next-generation sequencing is a methodology that can interrogate large regions of genomic DNA in a single assay. The presence and pattern of gene variants can provide critical diagnostic, prognostic, and therapeutic information for managing physicians.

 

Hereditary hemolytic anemias are caused by defects in one or more of the genes that control red blood cell (RBC) production, metabolism, or structure, resulting in faulty erythropoiesis, cell membranes, or enzymes required for normal RBC function.

 

This panel aids in the diagnosis and treatment for hereditary (congenital) hemolytic anemia.(1,2) The panel includes genes known to cause hereditary anemia, including those implicated in RBC enzyme,(3) RBC membrane/RBC hydration,(4,5) and congenital dyserythropoietic anemia(6) disorders. This panel can aid in the differential diagnosis of early onset and lifelong myopathic or neurologic syndromes, especially if associated with hemolysis. Specifically, this panel analyzes genes associated with hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, Southeast Asian ovalocytosis, hereditary stomatocytosis (both overhydrated and dehydrated/hereditary xerocytosis subtypes), and cryohydrocytosis. Hereditary stomatocytosis is an RBC membrane permeability disorder that can manifest as the more common dehydrated hereditary stomatocytosis, also known as hereditary xerocytosis, and the rarer overhydrated hereditary stomatocytosis subtypes. These disorders are important to confirm or exclude as splenectomy has been associated with an increased risk for serious venous thrombosis and thromboembolism events and is contraindicated in published guidelines.(2) It also includes genes associated with RBC enzymopathies, ranging from the common glucose 6-phosphate dehydrogenase and pyruvate kinase deficiencies to the rarer disorders of adenylate kinase, hexokinase, phosphofructokinase, phosphoglycerate kinase, pyruvate kinase, glutathione pathway, and triosephosphate isomerase.

 

This panel also includes multiple genes associated with congenital dyserythropoietic anemia (CDA), types 1a, 1b, 2, 3, and 4. CDA is a disorder of ineffective erythropoiesis associated with distinctive bone marrow morphologic changes.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(7) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Day(s) Performed

Varies

Report Available

28 to 42 days

Specimen Retention Time

Whole blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test 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.

CPT Code Information

81443

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NHHA Hereditary Hemolytic Anemia, NGS In Process

 

Result ID Test Result Name Result LOINC Value
619034 Test Description 62364-5
619035 Specimen 31208-2
619036 Source 31208-2
619037 Result Summary 50397-9
619038 Result 82939-0
619039 Interpretation 59465-5
619040 Additional Results 82939-0
619041 Resources 99622-3
619042 Additional Information 48767-8
619043 Method 85069-3
619044 Genes Analyzed 82939-0
619045 Disclaimer 62364-5
619046 Released By 18771-6