Test Catalog

Test Id : NGHHA

Hereditary Hemolytic Anemia Comprehensive Panel, Next-Generation Sequencing, 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 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

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

See Targeted Genes Interrogated by NGHHA Next-Generation Sequencing in Special Instructions for a list of the genes and exons targeted by this test.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See NGHHA and Subpanel Comparison Gene List in Special Instructions.

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

Hereditary Hemolytic Anemia Seq, V

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

Hereditary nonspherocytic hemolytic anemia

Congenital hemolytic anemia

Adenlyate kinase deficiency

AK

AK1

ALDOA

Aldolase A deficiency

ALDOA deficiency

ANK

ANK1

Ankyrin

C15ORF41

CDA

CDA type I

CDA type II

CDA type III

CDA type IV

CDAN1

Congenital dyserythropoietic anemia (CDA)

Congenital dyserythropoietic anemia type I

Congenital dyserythropoietic anemia type II

Congenital dyserythropoietic anemia type III

Congenital dyserythropoietic anemia type IV

Dehydrated hereditary stomatocytosis

Elliptocytosis

EPB41

EPB42

G6PD

G6PD deficiency

Gamma-glutamylcysteine synthetase deficiency

GATA1

GCLC

GCLC deficiency

Glucose phosphate isomerase deficiency

Glucose-6-phosphate-dehydrogenase deficiency

GLUT1

GLUT1 deficiency syndrome

Glutathione reductase deficiency

Glutathione synthetase deficiency

Glycolytic enzyme deficiencies

GPI

GPI deficiency

GSR

GSR deficiency

GSS

GSS deficiency

GYPC

HE type 1

HE type 2

HE type 3

HE type 4

Heme oxygenase 1 deficiency

Hereditary anemia

Hereditary elliptocytosis (HE)

Hereditary hemolytic anemia

Hereditary pyropoikilocytosis (HPP)

Hereditary spherocytosis (HS)

Hereditary xerocytosis

Hexokinase deficiency

HK

HK deficiency

HK1

HMOX 1 deficiency

HMOX1

HS type 1

HS type 2

HS type 3

HS type 4

HS type 5

KIF23

KLF1

NT5C3A

Ovalocytosis

P5NT

PFK

PFKM

PGK

PGK1

Phosphofructose kinase deficiency

Phosphoglycerate kinase 1 deficiency

Phosphoglycerate kinase deficiency

PIEZO1

PK

PK deficiency

PKLR

Protein 4.1

Protein 4.2

Pyrimidine 5' nucleotidase deficiency

Pyruvate kinase deficiency

RBC enzymopathies

RBC membrane disorders

RHAG

SEC23B

SLC2A1

SLC4A1

Southeast Asian ovalocytosis

Spectrin

SPTA

SPTA1

SPTB

STOM

Stomatocytosis

TPI

TPI deficiency

TPI1

Triosphosphate isomerase deficiency

Xerocytosis

Band3 subtype, Hereditary spherocytosis

Hereditary stomatocytosis (HSt)

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See NGHHA and Subpanel Comparison Gene List in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

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
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 (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 < 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. 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) 

2. 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: 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 (preferred)

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 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

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

See Targeted Genes Interrogated by NGHHA Next-Generation Sequencing in Special Instructions for a list of the genes and exons targeted by this test.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

See NGHHA and Subpanel Comparison Gene List in Special Instructions.

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 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
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.(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.

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 mutation that is not identified by the methods performed. The absence of a mutation, 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 (VAF) 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 pathogenic 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 insertion/deletion (indel) 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 polymorphisms may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion and 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. 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

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 assay is performed to test for the presence of a mutation in targeted regions of the following 39 genes: AK1, ALDOA, ANK1, C15ORF41, CD59, CDAN1, EPB41, EPB42, FANCA, FANCC, FANCG, G6PD, GATA1, GCLC, GPI, GSR, GSS, GYPC, HBB, HBD, HK1, HMOX1, KIF23, KLF1, NT5C3A, PFKM, PGK1, PIEZO1, PKLR, RHAG, RPS19, SEC23B, SLC2A1, SLC4A1, SPTA1, SPTB, STOM, TPI1, and UGT1A1. See Targeted Genes Interrogated by NGHHA Next-Generation Sequencing in Genetics Information in Special Instructions for details regarding the targeted gene regions identified by this test. This is a laboratory-developed test using Research Use Only reagents.

 

Next-generation sequencing (NGS) is performed using the Illumina MiSeq 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)

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

Test Id Test Order Name Order LOINC Value
NGHHA Hereditary Hemolytic Anemia Seq, V In Process
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
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 85069-3
40556 Disclaimer 62364-5
40558 Panel Gene List 36908-2
40559 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