Test Catalog

Test Id : NGENZ

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Red Blood Cell Enzyme Panel, Next-Generation Sequencing, Varies

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

For a list of the genes and exons targeted by this test, see Targeted Genes Interrogated by NGENZ Next-Generation Sequencing.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Next-Generation Sequencing (NGS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

RBC Enzyme Sequencing, V

Aliases
Lists additional common names for a test, as an aid in searching

AK

ALDOA

G6PD

GCLC

GPI

GSR

GSS

HK

HMOX1

P5NT

PFK

PGK

PK

PKLR

TPI

RBC enzymopathies

AK1

ALDOA deficiency

Aldolase A deficiency

G6PD deficiency

GCLC deficiency

GPI deficiency

GSR deficiency

GSS deficiency

Gamma-glutamylcysteine synthetase deficiency

Glucose phosphate isomerase deficiency

Glucose-6-phosphate-dehydrogenase deficiency

Glutathione reductase deficiency

Glutathione synthetase deficiency

Glycolytic enzyme deficiencies

HK deficiency

HK1

HMOX 1 deficiency

Hexokinase deficiency

NT5C3A

PFKM

PGK1

Phosphoglycerate kinase deficiency

Phosphoglycerate kinase 1 deficiency

Pyrimidine 5' nucleotidase deficiency

Pyruvate kinase deficiency

TPI deficiency

TPI1

Adenlylate kinase deficiency

Phosphofructo kinase deficiency

Triosephosphate isomerase deficiency

Specimen Type
Describes the specimen type validated for testing

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.

ORDER QUESTIONS AND ANSWERS

Question ID Description Answers
NGENS Specimen Type
NGEND Indication for Test

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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 < or =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 < or =30 days

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood, Bone Marrow: 1 mL

Extracted DNA: 100 mcL at 20 ng/mcL concentration

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

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

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

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

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

For a list of the genes and exons targeted by this test, see Targeted Genes Interrogated by NGENZ Next-Generation Sequencing.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

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.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical:

Some individuals may have a variant that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of hereditary hemolytic anemia or a related disorder. This assay does not distinguish between germline and somatic alterations, particularly with variant allele frequencies significantly lower than 50%. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If there is a family history of hereditary hemolytic anemia or a related disorder, it is often useful to test first-degree family members to help establish the clinical significance of variants of unknown significance.

 

At this time, it is not standard practice for the laboratory to systematically review likely disease-associated variants or variants of uncertain significance that have been previously detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Technical:

Some genetic or genomic alterations, such as large deletion/insertions (delin) events, copy number alterations and gene translocation events are not detected by this assay. The depth of coverage may be variable for some target regions, but assay performance below the minimum acceptable criteria or for failed regions will be noted. Additionally, rare variants (ie, polymorphisms) may be present that could lead to false negative or positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis. If the patient has had an allogenic blood transfusion, these results may be inaccurate due to the presence of donor DNA.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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 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. 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 May;17(5):405-424

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

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

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 10 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81443

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
NGENZ RBC Enzyme Sequencing, V In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
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

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports