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HelpTest ID: MEV1 Methemoglobinemia Evaluation, Blood
Shipping Instructions
Specimen must arrive within 3 days (72 hours) of collection.
Necessary Information
Include recent transfusion information.
Include most recent complete blood cell count results.
Metabolic Hematology Patient Information (T810) is strongly recommended. Testing may proceed without this information, however if the information requested is received, any pertinent reported clinical features and data will drive the focus of the evaluation and be considered in the interpretation.
The laboratory has extensive experience in hemoglobin variant identification and many cases can be confidently classified without molecular testing. However, molecular confirmation is always available, subject to sufficient sample quantity (eg, multiplex ligation-dependent probe amplification testing requires at least 2 mL of sample in addition to protein testing requirements). If no molecular testing or specific molecular tests are desired, utilize the appropriate check boxes on the form. If the form or other communication is not received, the reviewing hematopathologist will select appropriate tests to sufficiently explain the protein findings, which may or may not include molecular testing.
Specimen Required
The following specimens are required for testing:
Whole blood ACD-B specimen
2 Whole blood EDTA specimens
Container/Tube: Lavender top (EDTA) and yellow top (ACD solution B)
Specimen Volume:
EDTA: Two 4-mL tubes
ACD: One 6-mL tube
Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.
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:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Metabolic Hematology Patient Information (T810)
3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755) with the specimen
Useful For
Diagnosis of methemoglobinemia and sulfhemoglobinemia and possible hereditary (congenital) causes
Differentiation of methemoglobinemia and sulfhemoglobinemia from other causes of cyanosis (eg, congenital heart disease)
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MEVI | Methemoglobinemia Interpretation | No | Yes |
| HGBCE | Hb Variant, A2 and F Quantitation,B | Yes | Yes |
| HPLC | HPLC Hb Variant, B | No | Yes |
| METH | Methemoglobin, B | Yes, (Order MET) | Yes |
| SULF | Sulfhemoglobin, B | Yes, (Order MET) | Yes |
| METR1 | Cytochrome b5 Reductase, B | Yes | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| SDEX | Sickle Solubility, B | Yes | No |
| IEF | Isoelectric Focusing, B | No | No |
| MASS | Hb Variant by Mass Spec, B | No | No |
| UNHB | Hb Stability, B | No | No |
| HPFH | Hb F Distribution, B | No | No |
| ATHAL | Alpha-Globin Gene Analysis | Yes | No |
| WASQR | Alpha Globin Gene Sequencing, B | Yes, (Order WASEQ) | No |
| WBSQR | Beta Globin Gene Sequencing, B | Yes, (Order WBSEQ) | No |
| WBDDR | Beta Globin Cluster Locus Del/Dup,B | Yes, (Order WBDD) | No |
| WGSQR | Gamma Globin Full Gene Sequencing | Yes, (Order WGSEQ) | No |
| MEV0 | Methemoglobin Summary Interp | No | No |
Testing Algorithm
This is a consultative evaluation in which the case will be evaluated at Mayo Clinic Laboratories, the appropriate tests performed at an additional charge, and the results interpreted. This is an evaluation for methemoglobin and sulfhemoglobin levels and possible hereditary causes. Methemoglobin, sulfhemoglobin levels, cytochrome-b5 reductase (methemoglobin reductase) activity, and protein analysis screening for hemoglobin variants (capillary electrophoresis, cation exchange high performance liquid chromatography and capillary electrophoresis) will always be performed. If additional hemoglobin variant confirmatory testing is required, appropriate reflex testing will be performed. This will vary from additional protein analysis methods to molecular testing, as needed.
One or more of the following molecular tests may be reflexed:
-ATHAL / Alpha-Globin Gene Analysis, Varies
-WASQR / Alpha-Globin Gene Sequencing, Blood
-WBSQR / Beta-Globin Gene Sequencing, Blood
-WBDDR / Beta-Globin Cluster Locus Deletion/Duplication, Blood
-WGSQR / Gamma-Globin Full Gene Sequencing, Varies
After all test results are finalized, an additional consultative interpretation that summarizes all testing and incorporates subsequent genetic results will be provided.
For more information see Benign Hematology Evaluation Comparison.
Special Instructions
Method Name
MEVI, MEV0: Medical Interpretation
HGBCE: Capillary Electrophoresis
HPLC: Cation Exchange/High-Performance Liquid Chromatography (HPLC)
METH, SULF: Spectrophotometry (SP)
METR1: Kinetic Spectrophotometry
IEF: Isoelectric Focusing
HPFH: Flow Cytometry
UNHB: Isopropanol and Heat Stability
MASS: Mass Spectrometry (MS)
Reporting Name
Methemoglobinemia EvaluationSpecimen Type
Whole Blood ACD-BWhole Blood EDTA
Specimen Minimum Volume
EDTA blood: 3 mL
ACD blood: 2.7 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Whole Blood ACD-B | Refrigerated | 72 hours | |
| Whole Blood EDTA | Refrigerated | 72 hours |
Clinical Information
Methemoglobin:
Methemoglobin forms when the hemoglobin (Hb) molecule iron is in the ferric (Fe3[+]) form instead of the functional ferrous (Fe2[+]) 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.(1,2) Type IV is thought to be extraordinarily rare. Type III is no longer a category.
-One of several intrinsic structural disorders of Hb, called M-Hbs; all of which are inherited in an autosomal dominant manner.(3,4) Classically, M-Hbs 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 Hb 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:
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, acetanilide, phenacetin, trinitroluene, zinc ethylene bisdithiocarbamate (a fungicide), and flutamide. It is important to note that some Hb variants are known to interfere with this test (especially M-Hbs) and sulfhemoglobin absorbance can be increased due to the Hb variant. Hb 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
Definitive results and an interpretive report will be provided.
Interpretation
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.
Clinical Reference
1. OMIM: 250800 Methemoglobinemia due to deficiency of methemoglobin reductase. Updated May 20, 2019. Accessed January 23, 2024. Available at www.omim.org/entry/250800?search=250800&highlight=250800
2. OMIM: 250790 Methemoglobinemia and ambiguous genitalia. Updated December 9, 2022. Accessed January 23, 2024. Available at www.omim.org/entry/250790?search=250790&highlight=250790
3. OMIM: 141800 Hemoglobin alpha locus 1; HBA1. Updated September 15, 2023. Accessed January 23, 2024. Available at www.omim.org/entry/141800?search=141800&highlight=141800
4. OMIM: 141900 Hemoglobin beta locus; HBB. Updated September 15, 2023. Accessed January 23, 2024. 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, Levi MM, Press OW, Burns LJ, Caligiuri M, eds. Williams Hematology. 9th ed. McGraw-Hill; 2016: 789-800
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
83020-26-Hemoglobinopathy Interpretation
83020-Hb Variant, A2 and F Quantitation
83021-HPLC Hb Variant
82657-Methemoglobin reductase
83050-Methemoglobin, quantitative
83060-Sulfhemoglobin, quantitative
82664 (if appropriate)
83068 (if appropriate)
83789 (if appropriate)
88184 (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MEV1 | Methemoglobinemia Evaluation | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 8268 | Methemoglobin, B | 2614-6 |
| 8272 | Sulfhemoglobin, B | 4685-4 |
| 41927 | Hb A | 20572-4 |
| 65615 | HPLC Hb Variant, B | No LOINC Needed |
| METRB | Cytochrome b5 Reductase, B | 32703-1 |
| 608086 | Methemoglobinemia Interpretation | 59465-5 |
| 608108 | Reviewed By | 18771-6 |
| 41928 | Hb F | 32682-7 |
| 41929 | Hb A2 | 4552-6 |
| 41930 | Variant 1 | 24469-9 |
| 41931 | Variant 2 | 24469-9 |
| 41932 | Variant 3 | 24469-9 |
| 41933 | HGBCE Interpretation | 78748-1 |
Day(s) Performed
Monday through Saturday
Report Available
3 to 25 daysmml-benign-hematology-disorders