Test Catalog

Test Id : MEVI

Methemoglobinemia Interpretation

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

Interpretation of the methemoglobinemia evaluation results


Diagnosis of methemoglobinemia and sulfhemoglobinemia and possible hereditary (congenital) causes


Differentiation of methemoglobinemia and sulfhemoglobinemia from other causes of cyanosis (eg, congenital heart disease)

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

Only orderable as part of a profile. For more information see MEV1 / Methemoglobinemia Evaluation.


Medical Interpretation

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


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

Methemoglobinemia Interpretation

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

Cb5r deficiency

Congenital methaemoglobinemia

Congenital methemoglobinemia

cytochrome b5 reductase deficiency

Dominant congenital methemoglobinemia

Hemoglobin M

M Hemoglobins


Methemoglobin Evaluation

NADH cytochrome b5 reductase 3

NADH methemoglobin reductase deficiency


Recessive congenital methemoglobinemia


Specimen Type
Describes the specimen type validated for testing

Whole Blood EDTA

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
Whole Blood EDTA Refrigerated 72 hours

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

Interpretation of the methemoglobinemia evaluation results


Diagnosis of methemoglobinemia and sulfhemoglobinemia and possible hereditary (congenital) causes


Differentiation of methemoglobinemia and sulfhemoglobinemia from other causes of cyanosis (eg, congenital heart disease)

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


Methemoglobin forms when the hemoglobin molecule iron is in the ferric (Fe[3+]) form instead of the functional ferrous (Fe[2+]) form. Methemoglobinemia can be hereditary or acquired and is present by definition when methemoglobin levels are greater than the normal range. Acquired methemoglobinemia results after toxic exposure to nitrates and nitrites/nitrates (fertilizer, nitric oxide), topical anesthetics (“caines"), dapsone, naphthalene (moth balls/toilet deodorant cakes), and industrial use of aromatic compounds (aniline dyes).


Congenital methemoglobinemias are rare. They are due either to:

-A deficiency of cytochrome b5 reductase (methemoglobin reductase) in erythrocytes, an autosomal recessive disorder resulting from genetic variants in either CYB5R3 or CYB5A genes.(1,2) Type IV is thought to be extraordinarily rare. Type III is no longer a category.


-One of several intrinsic structural disorders of hemoglobin, called M-hemoglobins (M-Hb), all of which are inherited in an autosomal dominant manner.(3,4) Classically, M-Hb result from histidine-to-tyrosine substitutions at the proximal or distal histidine important in coordinating the oxygen molecule. These include alpha-, beta- and gamma-chain variants. Rarely, other substitutions outside the proximal and distal histidine location can cause hemoglobin variants that increase methemoglobin or sulfhemoglobin levels. Most M-Hb variants are readily identified by high-performance liquid chromatography (HPLC) or mass spectrometry methods with characteristic electrophoresis patterns; however, some require more specialized techniques. Most are associated with increased methemoglobin, with or without an increase in sulfhemoglobin. Alpha chain M-Hb variants can be associated with increased sulfhemoglobin without an increase in methemoglobin.



Sulfhemoglobin cannot combine with oxygen. When acquired, sulfhemoglobinemia can be associated with cyanosis and often accompanies methemoglobinemia. Sulfhemoglobinemia has been associated with exposure to sumatriptan, sulfonamides, metoclopramide, paint or varnish vapors, dimethyl sulfoxide (DMSO), acetanilide, phenacetin, trinitroluene, zinc ethylene bisdithiocarbamate (a fungicide), and flutamide. It is important to note that some hemoglobin variants are known to interfere with this test (especially M-Hb), and sulfhemoglobin absorbance can be increased due to the hemoglobin variant. Hemoglobin evaluation that includes the HPLC method is recommended to exclude this possibility.


In contrast to methemoglobinemia, sulfhemoglobinemia persists until the erythrocytes containing it are destroyed. Therefore, blood level of sulfhemoglobin declines gradually over a period of weeks.

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.

Only orderable as part of a profile. For more information see MEV1 / Methemoglobinemia Evaluation.


Definitive results and an interpretive report will be provided.

Provides information to assist in interpretation of the test results

This is a consultative evaluation in which the history and previous laboratory values are reviewed by a hematologist who is an expert on these disorders. Appropriate tests are performed and an interpretive report is issued.

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

Sulfhemoglobin is exceedingly stable and does not change in stored or shipped specimens.


Methemoglobin is unstable and can degrade at a rate of about 40% per 24 hours.


A normal methemoglobin value obtained with stored or shipped specimens does not exclude prior methemoglobinemia of minimal degree. However, significant methemoglobinemia will still be demonstrable.

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

1. OMIM: 250800 Methemoglobinemia due to deficiency of methemoglobin reductase. Updated May 20, 2019. Accessed October 19, 2020. Available at www.omim.org/entry/250800?search=250800&highlight=250800

2. OMIM: 250790 Methemoglobinemia and ambiguous genitalia. Updated May 18, 2018. Accessed October 19, 2020. Available at www.omim.org/entry/250790?search=250790&highlight=250790

3. OMIM: 141800 Hemoglobin alpha locus 1; HBA1. Updated November 1, 2019. Accessed October 19, 2020. Available at www.omim.org/entry/141800?search=141800&highlight=141800

4. OMIM: 141900 Hemoglobin beta locus; HBB. Updated November 14, 2019. Accessed October 19, 2020. Available at www.omim.org/entry/141900?search=141900&highlight=141900

5. Haymond S, Cariappa R, Eby CS, Scott MG: Laboratory assessment of oxygenation in methemoglobinemia. Clin Chem. 2005;51(2):434-444

6. Noor M, Beutler E: Acquired sulfhemoglobinemia. An underreported diagnosis? West J Med. 1998;169(6):386-389

7. Thom CS, Dickson CF, Gell DA, Weiss MJ: Hemoglobin variants: biochemical properties and clinical correlates. Cold Spring Harb Perspect Med. 2013;3(3):a011858

8. Percy MJ, McFerran NV, Lappin TR: Disorders of oxidized haemoglobin. Blood Rev. 2005;19(2):61-68

9. Agarwal AM, Prchal JT: Methemoglobinemia and other dyshemoglobinemias. In: Kaushansky K, Lichtman MA, Prchal JT, et al. eds. Williams Hematology. 9th ed. McGraw-Hill Book Company; 2016:789-800

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

A hematopathologist who is an expert in these disorders evaluates the case and an interpretive report is issued.

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


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 through Friday

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.

3 to 25 days

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


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.

Not Applicable

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.


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
MEVI Methemoglobinemia Interpretation 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.
608086 Methemoglobinemia Interpretation 59465-5
608108 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