Test Id : BPGMM
2,3-Bisphosphoglycerate Mutase, Full Gene Sequencing Analysis, Varies
Useful For
Suggests clinical disorders or settings where the test may be helpful
Diagnosing 2,3-bisphosphoglycerate mutase deficiency in individuals with lifelong, unexplained erythrocytosis
Identifying genetic variant carriers in family members of an affected individual for the purposes of preconception genetic counseling
This test is not intended for prenatal diagnosis.
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
The BPGM gene encodes the enzyme 2,3-bisphosphoglycerate mutase (BPGM) that catalyzes the conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate (2,3-BPG), also known as 2,3-diphosphoglycerate (2,3-DPG), through the Luebering-Rapoport pathway. 2,3-BPG is a small molecule generated from glycolysis and is present in large amounts in red blood cells. It functions to stabilize the hemoglobin molecule and facilitates oxygen unloading at tissue sites. Therefore, 2,3-BPG concentrations affect the oxygen affinity of hemoglobin. Variations in this gene that result in a deficiency of 2,3-BPG can cause hereditary erythrocytosis.
This test can detect variants in BPGM that are associated with unexplained lifelong erythrocytosis due to bisphosphoglycerate mutase deficiency.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
This evaluation is recommended for patients presenting with lifelong elevation in hemoglobin or hematocrit, usually with a positive family history of similar symptoms. Reported cases of 2,3- bisphosphoglycerate deficiency have been associated with decreased p50 values (left-shifted oxygen-dissociation curve). Due to the rarity of this disorder, other more common causes of erythrocytosis should be excluded prior to ordering; for more information see Erythrocytosis Evaluation Testing Algorithm .
Polycythemia vera and chronic myeloproliferative neoplasm should be excluded prior to testing as they are more common causes of elevated hemoglobin values. A JAK2 V617F or JAK2 exon 12 variant should not be present. Patient serum erythropoietin levels are typically normal or elevated.
Method Name
A short description of the method used to perform the test
Polymerase Chain Reaction (PCR)/Sanger Sequencing
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
Aliases
Lists additional common names for a test, as an aid in searching
DPGM, 2,3-bisphosphoglycerate mutase
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
This evaluation is recommended for patients presenting with lifelong elevation in hemoglobin or hematocrit, usually with a positive family history of similar symptoms. Reported cases of 2,3- bisphosphoglycerate deficiency have been associated with decreased p50 values (left-shifted oxygen-dissociation curve). Due to the rarity of this disorder, other more common causes of erythrocytosis should be excluded prior to ordering; for more information see Erythrocytosis Evaluation Testing Algorithm .
Polycythemia vera and chronic myeloproliferative neoplasm should be excluded prior to testing as they are more common causes of elevated hemoglobin values. A JAK2 V617F or JAK2 exon 12 variant should not be present. Patient serum erythropoietin levels are typically normal or elevated.
Specimen Type
Describes the specimen type validated for testing
Varies
Ordering Guidance
This test detects variants identifiable by Sanger sequencing in the BPGM gene only. For a reflexive evaluation including hemoglobin electrophoresis and variant analysis of genes associated with hereditary erythrocytosis, order REVE2 / Erythrocytosis Evaluation, Blood.
This test does not provide a serum erythropoietin (EPO) level. If EPO testing is desired, order EPO / Erythropoietin, Serum.
Necessary Information
Erythrocytosis Patient Information (T694) is strongly recommended, but not required, to be filled out and sent with the specimen. This information aids in providing a more thorough interpretation of test results. Ordering providers are strongly encouraged to complete the form and send it with the specimen.
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:
Patient Preparation: Bone marrow transplants preclude accurate germline and genetic variant analysis. Inform the laboratory if this patient has undergone bone marrow transplantation. On rare occasions transfusion of blood products can preclude accurate genetic variant analysis, and results should be interpreted with caution if performed after recent transfusion (within 4 months).
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD), green top (sodium heparin)
Specimen Volume: 4 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in the original tube. Do not aliquot
Specimen Stability Information: Ambient 14 days (preferred)/Refrigerate 30 days
Specimen Type: Extracted DNA from whole blood
Container/Tube: 1.5 to 2 mL tube
Specimen Volume: Entire specimen
Collection Instructions:
1. Label specimen as extracted DNA and source of specimen
2. Provide volume and concentration of the DNA
Specimen Stability Information: Frozen (preferred)/Refrigerate/Ambient
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:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Erythrocytosis Patient Information (T694)
3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request Form (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. The minimum volume is sufficient for one attempt at testing.
Blood: 1 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Bone marrow Paraffin-embedded tissue Frozen tissue Paraffin-embedded bone marrow aspirate clot Methanol-acetic acid (MAA)-fixed pellets Moderately to severely clotted | 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
Diagnosing 2,3-bisphosphoglycerate mutase deficiency in individuals with lifelong, unexplained erythrocytosis
Identifying genetic variant carriers in family members of an affected individual for the purposes of preconception genetic counseling
This test is not intended for prenatal diagnosis.
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
The BPGM gene encodes the enzyme 2,3-bisphosphoglycerate mutase (BPGM) that catalyzes the conversion of 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate (2,3-BPG), also known as 2,3-diphosphoglycerate (2,3-DPG), through the Luebering-Rapoport pathway. 2,3-BPG is a small molecule generated from glycolysis and is present in large amounts in red blood cells. It functions to stabilize the hemoglobin molecule and facilitates oxygen unloading at tissue sites. Therefore, 2,3-BPG concentrations affect the oxygen affinity of hemoglobin. Variations in this gene that result in a deficiency of 2,3-BPG can cause hereditary erythrocytosis.
This test can detect variants in BPGM that are associated with unexplained lifelong erythrocytosis due to bisphosphoglycerate mutase deficiency.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
This evaluation is recommended for patients presenting with lifelong elevation in hemoglobin or hematocrit, usually with a positive family history of similar symptoms. Reported cases of 2,3- bisphosphoglycerate deficiency have been associated with decreased p50 values (left-shifted oxygen-dissociation curve). Due to the rarity of this disorder, other more common causes of erythrocytosis should be excluded prior to ordering; for more information see Erythrocytosis Evaluation Testing Algorithm .
Polycythemia vera and chronic myeloproliferative neoplasm should be excluded prior to testing as they are more common causes of elevated hemoglobin values. A JAK2 V617F or JAK2 exon 12 variant should not be present. Patient serum erythropoietin levels are typically normal or elevated.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Erythrocytosis (ie, increased red blood cell mass and elevated hemoglobin and hematocrit) may be primary, due to an intrinsic defect of bone marrow stem cells as in polycythemia vera (PV), or secondary, in response to increased serum erythropoietin (EPO) levels. Secondary erythrocytosis is associated with a number of disorders including chronic lung disease, chronic increase in carbon monoxide, cyanotic heart disease, high-altitude living, kidney cysts and tumors, hepatoma, and other EPO-secreting tumors. When these common causes of secondary erythrocytosis are excluded, a heritable cause involving hemoglobin or erythrocyte regulatory mechanism may be suspected.
Unlike PV, hereditary erythrocytosis is not associated with the risk of clonal evolution and most commonly presents as isolated erythrocytosis that has been present since childhood. Hereditary erythrocytosis may be caused by alterations in one of several genes and inherited in either an autosomal dominant or autosomal recessive manner.
Genetic variants causing hereditary erythrocytosis have been found in genes coding for alpha and beta hemoglobins, hemoglobin stabilization proteins (eg, 2,3-bisphosphoglycerate mutase: BPGM), the erythropoietin receptor (EPOR), and oxygen-sensing pathway enzymes (hypoxia-inducible factor: HIF, prolyl hydroxylase domain: PHD, and von Hippel Lindau: VHL), see Table. The true prevalence of variants causing hereditary erythrocytosis is unknown; however, very few cases of 2,3-BPG deficiency-associated hereditary erythrocytosis have been identified, and this disorder is thought to be rare.
Table. Erythrocytosis Testing
| Gene | Inheritance | Serum EPO |
| JAK2 V617F | Acquired | Decreased |
| JAK2 exon 12 | Acquired | Decreased |
| EPOR | Dominant | Decreased |
| PHD2/EGLN1 | Dominant | Normal |
| BPGM | Recessive | Normal |
| Beta globin | Dominant | Normal to increased |
| Alpha globin | Dominant | Normal to increased |
| HIF2A/EPAS1 | Dominant | Normal to increased |
| VHL | Recessive | Normal to increased |
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
An interpretive report will be provided and will include specimen information, assay information, and whether the specimen was positive for any variations in the gene. If positive, the alteration will be correlated with clinical significance, if known.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test does not detect large deletions and duplications in BPGM.
Polycythemia vera and acquired causes of erythrocytosis should be excluded before ordering this test.
Certain genetic alterations have no clinical manifestations and, in essence, are clinically benign. Correlation with all relevant clinical information is necessary to provide appropriate patient care.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Petousi N, Copley RR, Lappin TR, et al: Erythrocytosis associated with a novel missense mutation in the BPGM gene. Haematologica. 2014 Oct;99(10):e201-e204
2. Hoyer JD, Allen SL, Beutler E, Kubik K, West C, Fairbanks VF: Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Am J Hematol. 2004 Apr;75(4):205-208
3. Rosa R, Prehu MO, Beuzard Y, Rosa J: The first case of a complete deficiency of diphosphoglycerate mutase in human erythrocytes. J Clin Invest. 1978 Nov;62(5):907-915
Method Description
Describes how the test is performed and provides a method-specific reference
DNA is extracted from whole peripheral blood and amplified in 4 separate polymerase chain reactions (PCR) to cover BPGM exons 1 through 4. PCR products are then sequenced by the Sanger sequencing method and analyzed with sequencing software. Patient sequence results are compared with the genomic reference sequences and the single-nucleotide variants known to occur in the genes. If a variant is detected, the messenger RNA reference sequence will be used to determine the amino acid number and resulting amino acid change if there is one.(Lemarchandel V, Joulin V: Compound heterozygosity in a complete erythrocyte bisphosphoglycerate mutase deficiency. Blood. 1992 Nov;80[10]:2643-2649; McMullin MF: Congenital erythrocytosis. IJLH 2016;38[Suppl. 1]:59-65)
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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.
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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. It 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.
CPT codes are provided by the performing laboratory.
81479
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 |
|---|---|---|
| BPGMM | BPGM Full Gene Sequencing | 94190-6 |
| 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.
|
|---|---|---|
| 37111 | BPGM Gene Sequencing Result | No LOINC Needed |
| 37112 | BPGM Interpretation | 69047-9 |