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Test Code MISC2MAYONGENZ Red Blood Cell Enzyme Panel, Next-Generation Sequencing, Varies

Secondary ID

64937

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

Method Name

Next-Generation Sequencing (NGS)

Reporting Name

RBC Enzyme Sequencing, V

Specimen Type

Varies


Ordering Guidance


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



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 panel always should be interpreted in the context of protein functional findings by enzymatic assay and complete blood count and peripheral blood findings. This complete interpretation can be provided by also ordering the EEEV1 / RBC Enzyme Evaluation. Please fill out the information sheet and indicate that a next-generation sequencing test was ordered. Providing complete blood cell count data and clinical notes will also allow more precise interpretation of results.



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. 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 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 or (ACD)

Acceptable: Green top (heparin)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot

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, Bone Marrow: 1 mL
Extracted DNA: 100 mcL at 20 ng/mcL concentration

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

Gross hemolysis Reject
Gross lipemia OK
Bone marrow biopsies
Slides
Paraffin shavings
Frozen tissues
Paraffin-embedded tissues
Paraffin-embedded bone marrow aspirates
Reject

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 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. 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

Evaluation and categorization of variants is performed using the most recent published American College of Medical Genetics recommendations as a guideline.(4) 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.

Method Description

This next-generation sequencing (NGS) assay is performed to test for the presence of a pathogenic variant in targeted regions of 17 genes. See Targeted Genes Interrogated by NGENZ Next-Generation Sequencing for details regarding the targeted gene regions identified by this test. This is a laboratory-developed test.

 

NGS is performed using a Illumina instrument with paired-end, 151-base pair (bp) reads. The DNA is prepared for NGS using a custom Agilent SureSelect Target Enrichment System. Data is analyzed with the CLC Genomics Server Program. Supplemental or confirmatory Sanger sequencing is performed when necessary.(Unpublished Mayo method)

 

Genes analyzed: AK1, ALDOA, G6PD, GCLC, GPI, GSR, GSS, HBB, HBD, HK1, HMOX1, NT5C3A, PFKM, PGK1, PKLR, TPI1, and UGT1A1

Day(s) Performed

Monday

Report Available

8 to 10 weeks

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. This test 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
NGENZ RBC Enzyme Sequencing, V In Process

 

Result ID Test Result Name Result LOINC Value
NGENS Specimen Type 31208-2
NGEND Indication for Test 42349-1
40560 Alterations Detected 82939-0
40561 Interpretation 59465-5
40562 Additional Notes 48767-8
40563 Method Summary 85069-3
40564 Disclaimer 62364-5
40566 Panel Gene List 36908-2
40567 Reviewed By 18771-6

Forms

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

2. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file.

-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.