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Test ID: NGHHA Hereditary Hemolytic Anemia Comprehensive Panel, Next-Generation Sequencing, Varies

Useful For

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

 

Comprehensive testing for patients in whom previous targeted gene mutation 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 mutations within genes associated with phenotypic severity, allowing for predictive testing and further genetic counseling

Method Name

Next-Generation Sequencing (NGS)

Reporting Name

Hereditary Hemolytic Anemia Seq, V

Specimen Type

Varies


Shipping Instructions


Peripheral blood specimens must arrive within 30 days of collection.



Necessary Information


1. Metabolic Hematology Next-Generation Sequencing (NGS) Patient Information is required, see Special Instructions. 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, CBC results and relevant clinical notes) and differentials based on clinical or morphologic presentation.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Peripheral blood (preferred)

Container/Tube:

Preferred: Lavender top (EDTA) or Yellow top (ACD)

Acceptable: Green top (heparin)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

3. Label specimen as blood.

Specimen Stability: Refrigerated ≤30 days

 

Specimen Type: Extracted DNA

Container/Tube: 1.5- to 2-mL tube

Specimen Volume: Entire specimen

Collection Instructions:

1. Indicate volume and concentration of the DNA.

2. Label specimen as extracted DNA and source of specimen.

Specimen Stability: Frozen/Refrigerated/Ambient ≤30 days


Specimen Minimum Volume

Blood: 1 mL
Extracted DNA: 100 mcL at 20 ng/mcL concentration

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

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

 

This test is best interpreted in the context of protein studies and peripheral blood findings. This can be provided by ordering the HAEVP / Hemolytic Anemia Evaluation Profile test. Please fill out the information sheet and indicate that NGS testing was also ordered. Providing CBC data and clinical notes will also allow more precise interpretation of results.

 

Hereditary hemolytic anemias are caused by defects in one or more of the genes that control 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) and congenital dyserythropoietic anemia(5) 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 assays genes associated with hereditary spherocytosis (HS), hereditary elliptocytosis (HE), hereditary pyropoikilocytosis (HPP), Southeast Asian ovalocytosis, hereditary stomatocytosis (both overhydrated and dehydrated/hereditary xerocytosis subtypes), and cryohydrocytosis. Hereditary stomatocytosis is a RBC membrane permeability disorder that can manifest as the more common dehydrated hereditary stomatocytosis (DHSt), also known as hereditary xerocytosis (HX) and the rarer overhydrated hereditary stomatocytosis (OHSt) 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.(7) It also includes genes associated with RBC enzymopathies, ranging from the common glucose 6 phosphate dehydrogenase (G6PD) and pyruvate kinase (PK) deficiencies, to the rarer disorders of adenylate kinase (AK1), hexokinase (HK1), phosphofructokinase (PFKM), phosphoglycerate kinase (PGK1), pyruvate kinase (PKLR), glutathione pathway, and triosephosphate isomerase (TPI1).

 

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. A limited number of the most common genes associated with Fanconi anemia (FA) and Diamond-Blackfan anemia (DBA) are also analyzed by this panel; however, this panel is not intended as a thorough investigation of FA or DBA.

Reference Values

An interpretive report will be provided.

Interpretation

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics recommendations as a guideline.(6,7) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and predictions made by these tools may change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Clinical Reference

1. Nathan and Oski's Hematology of Infancy and Childhood. Edited by SH Orkin, DG Nathan, D Ginsburg, et al. Seventh edition. Philadelphia, Saunders Elsevier, 2009, pp 455-1108

2. Iolascon A, Andolfo I, Barcellini W, et al: Recommendations for splenectomy in hereditary hemolytic anemias. Haematologica 2017 May 26. PMID: 28550188. doi: 10.3324/haematol.2016.161166.

3. Koralkova P, van Solinge WW, van Wijk R: Rare hereditary red blood cell enzymopathies associated with hemolytic anemia - pathophysiology, clinical aspects, and laboratory diagnosis. Int J Lab Hematol 2014 Jun;36(3):388-397

4. King MJ, Garçon L, Hoyer JD, et al: International Council for Standardization in Haematology. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol 2015 Jun;37(3):304-325

5 Gambale A, Iolascon A, Andolfo I, Russo R: Diagnosis and management of congenital dyserythropoietic anemias. Expert Rev Hematol 2016 Mar;9(3):283-296

6. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-424

Day(s) and Time(s) Performed

Monday

Analytic Time

8 weeks

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81443

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NGHHA Hereditary Hemolytic Anemia Seq, V In Process

 

Result ID Test Result Name Result LOINC Value
NGHHS Specimen Type 31208-2
NGHHD Indication for Test 42349-1
40552 Alterations Detected 82939-0
40553 Interpretation 59465-5
40554 Additional Notes 48767-8
40555 Method Summary 49549-9
40556 Disclaimer 62364-5
40558 Panel Gene List 36908-2
40559 Reviewed By 18771-6

Forms

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) 

Testing Algorithm

See NGHHA and Subpanel Comparison Gene List in Special Instructions.

Mayo Clinic Laboratories | Hematology Catalog Additional Information:

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