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Test ID NCYB Recessive Congenital Methemoglobinemia, CYB5 and CYB5 Reductase Genetic Analysis, Next-Generation Sequencing, Varies

Ordering Guidance

This test should be performed after more common causes of methemoglobinemia have been eliminated. To assess for more common causes of methemoglobinemia, order MEV1 / Methemoglobinemia Evaluation, Blood.


Testing for the CYB5A and CYB5R3 genes as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.


Multiple gene panels are available. For more information see NHEP and Subpanel Comparison Gene List.


Targeted testing for familial variants (also called site-specific or known variants testing) is available for the CYB5A and CYB5R3 genes. See FMTT / Familial Mutation, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Additional Testing Requirements

This test is best interpreted in the context of protein functional findings by enzymatic assay and complete blood cell count analysis. This complete interpretation can be provided by also ordering the MEV1 / Methemoglobinemia Evaluation, Blood. Fill out the information sheet and indicate that a next-generation sequencing test was also ordered. Providing complete blood cell count data and clinical notes will also allow 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 clinical presentation and/or laboratory findings.

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.


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


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 genetic evaluation for patients with a personal or family history suggestive of recessive congenital methemoglobinemia


Genotype confirmation of borderline cytochrome b5 reductase (methemoglobin reductase: METR) enzyme activity levels


Identifying variants within the CYB5 and CYB5 reductase genes (CYB5A, CYB5R3) allowing for further genetic counseling

Testing Algorithm

Genetic testing for congenital methemoglobinemia is indicated if:

-There is cyanosis in the setting of clinically stable patient ("more blue than sick")

-Methemoglobin reductase (cytochrome b5 reductase) activity is decreased

-Hemoglobin electrophoresis, particularly high-performance liquid chromatography testing, is negative

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

CYB5 and CYB5 Reductase, NGS

Specimen Type


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reference Values

An interpretive report will be provided.

Day(s) Performed


Report Available

28 to 42 days

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


LOINC Code Information

Test ID Test Order Name Order LOINC Value
NCYB CYB5 and CYB5 Reductase, NGS In Process


Result ID Test Result Name Result LOINC Value
618978 Test Description 62364-5
618979 Specimen 31208-2
618980 Source 31208-2
618981 Result Summary 50397-9
618982 Result 82939-0
618983 Interpretation 59465-5
618984 Additional Results In Process
618985 Resources 99622-3
618986 Additional Information 48767-8
618987 Method 85069-3
618988 Genes Analyzed 82939-0
618989 Disclaimer 62364-5
618990 Released By 18771-6