Diagnosis of 2,3-bisphosphoglycerate mutase deficiency in individuals with lifelong, unexplained erythrocytosis
Identifying mutation carriers in family members of an affected individual for the purposes of preconception genetic counseling
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. Mutations in this gene that result in a deficiency of 2,3-BPG can cause hereditary erythrocytosis.
This test can detect mutations in BPGM that are associated with unexplained lifelong erythrocytosis due to bisphosphoglycerate mutase deficiency.
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-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 mutation 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 mutation analysis of genes associated with hereditary erythrocytosis, order REVE / Erythrocytosis Evaluation.
