Test Catalog

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

Diagnosis of 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 (BPG) 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; see Erythrocytosis Evaluation Testing Algorithm in Special Instructions.

 

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 and oxygen dissociation p50 values decreased in test candidates. For a reflexive evaluation including p50 testing, hemoglobin electrophoresis, and variant analysis of genes associated with hereditary erythrocytosis, order REVE1 / Erythrocytosis Evaluation, Whole Blood.

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

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.

Yes

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

BPGM Full Gene Sequencing

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 (BPG) 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; see Erythrocytosis Evaluation Testing Algorithm in Special Instructions.

 

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 and oxygen dissociation p50 values decreased in test candidates. For a reflexive evaluation including p50 testing, hemoglobin electrophoresis, and variant analysis of genes associated with hereditary erythrocytosis, order REVE1 / Erythrocytosis Evaluation, Whole Blood.

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 complete evaluation in an algorithmic fashion, order REVE1 / Erythrocytosis Evaluation, Whole Blood.

 

This test does not provide a serum erythropoietin (EPO) level. If EPO testing is desired, order EPO / Erythropoietin, Serum.

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. Please 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: Peripheral 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 specimen in the original tube.

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 in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Erythrocytosis Patient Information (T694) in Special Instructions

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

Blood: 1 mL

Extracted DNA: 50 mcL at 50 ng/mcL concentration

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 (preferred)

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

Diagnosis of 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 (BPG) 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; see Erythrocytosis Evaluation Testing Algorithm in Special Instructions.

 

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 and oxygen dissociation p50 values decreased in test candidates. For a reflexive evaluation including p50 testing, hemoglobin electrophoresis, and variant analysis of genes associated with hereditary erythrocytosis, order REVE1 / Erythrocytosis Evaluation, Whole Blood.

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, renal 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. High-oxygen-affinity hemoglobin variants and BPGM abnormalities result in a decreased p50 result, whereas those affecting EPOR, HIF, PHD, and VHL have normal p50 results. 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.

 

Erythrocytosis Testing

Gene

Inheritance

Serum Epo

p50

JAK2 V617F

Acquired

Decreased

Normal

JAK2 exon 12

Acquired

Decreased

Normal

EPOR

Dominant

Decreased

Normal

PHD2/EGLN1

Dominant

Normal

Normal to mildly decreased

BPGM

Recessive

Normal

Decreased

Beta globin

Dominant

Normal to increased

Decreased

Alpha globin

Dominant

Normal to increased

Decreased

HIF2A/EPAS1

Dominant

Normal to increased

Normal

VHL

Recessive

Normal to increased

Normal

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. The p50 value should be decreased.

 

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:e201-e204

2. Hoyer JD, Allen SL, Beutler E, et al: Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Am J Hematol. 2004;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;62(5):907-915

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

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

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 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.

10 to 25 days

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.

81479-Unlisted Molecular Pathology procedure

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