Home
HelpTest ID: NENZ Red Blood Cell Enzyme Disorders 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 is 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 panel aids in the diagnosis and genetic counseling of individuals with inherited red blood cell enzymopathies, possible carrier states, or compound variants with severity modulating interactions. This test is best interpreted in the context of protein functional findings by enzymatic assay, complete blood cell count, and peripheral blood findings. This complete interpretation can be provided by also ordering the EEEV1 / Red Blood Cell (RBC) Enzyme Evaluation, Blood or HAEV1 / Hemolytic Anemia Evaluation, 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.
Useful For
Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of an underlying red blood cell enzymopathy
Identifying variants within genes associated with phenotypic severity, allowing for predictive testing and further genetic counseling
Special Instructions
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
RBC Enzyme Sequencing, NGSSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
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.
Mature erythrocytes are dependent upon glycolysis for energy production and the hexose monophosphate shunt for oxidation-reduction stability. Hereditary deficiencies in red blood cell (RBC) enzymes within these pathways cause nonspherocytic hemolytic anemia with variable clinical presentations, therapeutic considerations, and inheritance patterns.(1-3) Most of these deficiencies cause chronic hemolysis with little to no pathognomonic morphologic changes in the peripheral blood smear, making correlation with enzyme activity critical for diagnosis. Some are associated with acute episodic anemia triggered by medications, food, or viral illness. Variable additional symptoms may be present for some deficiency types, including myopathy, neuropathy, and developmental delay. Because a subset of clinically significant RBC enzyme disorders can have indeterminate to normal enzyme activity (masking in the presence of increased reticulocytes), the protein (enzymatic activity) studies are more sensitive when performed as a panel of RBC enzymes, which allows comparison of multiple enzyme activities. This genetic panel can aid in the interpretation of equivocal protein findings and genetically confirm an enzyme deficiency, especially if the patient has been recently transfused with red blood cells. Additionally, there are genes interrogated on this panel for which an enzyme test is not clinically available for correlation.
Reference Values
An interpretive report will be provided.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(5) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Orkin SH, Nathan DG, Ginsburg D, et al, eds. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Saunders Elsevier; 2009:360-364
2. Iolascon A, Andolfo I, Barcellini W, et al. Recommendations for splenectomy in hereditary hemolytic anemias. Haematologica. 2017;102(8):1304-1313. 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;36(3):388-397
4. Zanella A, Fermo E, Bianchi P, Chiarelli LR, Valentini G. Pyruvate kinase deficiency: the genotype-phenotype association. Blood Rev. 2007;21(4):217-231. doi:10.1016/j.blre.2007.01.001
5. Richards S, Aziz N, Bale S, et al. ACMG Laboratory Quality Assurance Committee: 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(5):405-424
Day(s) Performed
Varies
Report Available
28 to 42 daysTest 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 |
|---|---|---|
| NENZ | RBC Enzyme Sequencing, NGS | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 619048 | Test Description | 62364-5 |
| 619049 | Specimen | 31208-2 |
| 619050 | Source | 31208-2 |
| 619051 | Result Summary | 50397-9 |
| 619052 | Result | 82939-0 |
| 619053 | Interpretation | 59465-5 |
| 619054 | Additional Results | 82939-0 |
| 619055 | Resources | 99622-3 |
| 619056 | Additional Information | 48767-8 |
| 619057 | Method | 85069-3 |
| 619058 | Genes Analyzed | 82939-0 |
| 619059 | Disclaimer | 62364-5 |
| 619060 | Released By | 18771-6 |
mml-benign-hematology-disorders