Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
A 28-year-old asymptomatic male of Iranian Jewish (Meshadi) heritage was found on routine exam to have an erythrocytosis (RBC = 6.22 x 10(12)/l, Hgb = 19.2 g/dl, Hct = 58.9%). Splenomegaly was absent on physical exam. There was no family history of erythrocytosis. His oxygen dissociation curve was left-shifted with a p50 of 19 mmHg (normal = 25-32 mmHg). Hemoglobin electrophoresis showed no abnormalities. DNA sequencing of the hemoglobin beta globin gene and both alpha globin genes did not reveal a mutation. A 2,3-bisphosphoglycerate (BPG) level was markedly decreased at 0.3 micromol/g Hb (normal = 11.4-19.4 micromol/g Hb). The patient's bisphosphoglycerate mutase (BPGM) enzyme activity was also markedly decreased at 0.16 IU/g Hb (normal = 4.13-5.43 IU/g Hb). A red cell enzyme panel revealed a markedly decreased G-6-PD level (0.3 U/g Hb, normal = 8.6-18.6 U/g Hb). His parents and a brother were also available for evaluation. Both parents showed normal 2,3-BPG levels but BPGM activity approximately 50% of normal. Paradoxically, the brother showed normal BPGM activity but a slightly decreased 2,3-BPG level. All family members had markedly decreased G-6-PD activity. DNA sequencing of the BPGM gene showed the propositus to be homozygous for 185 G-->A, Arg 62 Gln in exon 2. Thus, the erythrocytosis in this patient is secondary to low 2,3-BPG levels, due to a deficiency in BPG mutase. This appears due to consanguinity within this family.
Hoyer
James D
JD
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. jhoyer@mayo.edu
Allen
Steven L
SL
Beutler
Ernest
E
Kubik
Kathleen
K
West
Carol
C
Fairbanks
Virgil F
VF
D000328:Adult; D001731:Bisphosphoglycerate Mutase / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications*; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D010290:Parents; D011086:Polycythemia / Q000097:blood / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D035781:Siblings
D001731:Bisphosphoglycerate Mutase; D010100:Oxygen