title: Symptomatic erythrocytosis associated with a compound heterozygosity for Hb Lepore-Boston-Washington (δ87-β116) and Hb Johnstown [β109(G11)Val→Leu, GTG>TTG].
abstract: Hb Johnstown [β109(G11)Val→Leu, GTG>TTG] has previously been described as a high oxygen affinity variant in a heterozygous state and in combination with β(0)-thalassemia (β(0)-thal). Because the variant does not separate from Hb A by routine methods it may be easily missed unless clinical suspicion is high. Hb Lepore-Boston-Washington (Hb LBW; δ87-β116) is a δβ hybrid variant that clinically manifests similarly to a β(+)-thal. Hb LBW is not detected by routine polymerase chain reaction (PCR) sequencing but is easily detected by electrophoretic methods. We describe a 19-year-old African American male with a compound heterozygosity for Hb Johnstown and Hb LBW. The patient presented with progressively worsening chest pains, headaches and erythrocytosis. He was repeatedly phlebotomized with symptomatic improvement and subsequently was confirmed to have the high oxygen affinity hemoglobin (Hb) variant. The lowest Hb and hematocrit (packed cell volume, PCV) achieved by phlebotomy was 16.1 g/dL and 0.51 L/L, respectively. Currently, he is no longer being phlebotomized, and is feeling relatively well except for minor chest pain. It is unclear to what degree the phlebotomies contributed to his subjective improvement. The combination of Hbs Johnstown and LBW has not been heretofore described, and in this case, was associated with marked symptomatic erythrocytosis. This unique combination results in a more pronounced phenotype, similar to or slightly more severe than, compound Hb Johnstown/β(0)-thal. This compound hemoglobinopathy will likely not be correctly classified using a single method of Hb detection and underscores the need for multiple characterization methods when indicated by the clinical picture.
authors.affiliation: Department of Pediatrics, Hurley Medical Center, Flint, Michigan 48503, USA. sinoue1@hurleymc.com
authors.forename: Susumu
authors.initials: S
authors.lastname: Inoue
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Oliveira
authors.forename: James D
authors.initials: JD
authors.lastname: Hoyer
authors.forename: Mahesh
authors.initials: M
authors.lastname: Sharman
mesh_terms: D001483:Base Sequence; D002637:Chest Pain / Q000209:etiology; D006261:Headache / Q000209:etiology; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D018962:Phlebotomy; D011086:Polycythemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; C066866:hemoglobin Johnstown; C039800:hemoglobin Lepore Boston-Washington