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Hemoglobin Wayne Trait with Incidental Polycythemia

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Hemoglobin Wayne Trait with Incidental Polycythemia Available online at www.annclinlabsci.org 96 Annals of Clinical & Laboratory Science, vol. 47, no. 1, 2017 Hemoglobin Wayne Trait with Incidental Polycythemia Manju Ambelil, Nghia Nguyen, Amitava Dasgupta, Semyon Risin, and Amer Wahed Department of Pathology and Laboratory Medicine, University of Texas Health Science Center- McGovern Medical School, Houston, TX, USA Abstract. Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain he- moglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne. Since the patient was not homozygous for hemoglobin Wayne, which is associated with second- ary polycythemia, the laboratory diagnosis in this case was critical in ruling out hemoglobinopathy as the etiology of his polycythemia. Key words: Hemoglobinopathies; hemoglobin Wayne; alpha globin chain variant. Introduction mean corpuscular hemoglobin of 27.1 pg. The red cell distribution width, total and differential leukocyte Hemoglobinopathies are the most common and counts, and platelets were normal. An anemia study clinically significant single-gene-inherited disorders showed a serum iron level of 127 mcg/dL, a ferritin con- [1]. These are caused by mutations in the globin centration of 239 ng/mL, an iron saturation of 42%, a total iron binding capacity of 306 mcg/dL, an unsatu- genes, resulting in quantitative and qualitative de- rated iron binding capacity of 179mcg/dL, and a vita- fects in the globin chain synthesis [2]. Analysis of min B12 level of 549pg/mL. Sequence analyses of JAK2 hemoglobin (Hb) by electrophoresis and high per- V617F, JAK2 exon 12, and JAK2 exon 13 were formance liquid chromatography (HPLC) are the negative. commonly used methods to support the diagnosis of hemoglobinopathies, however, occasional Hb Hemoglobin evaluation using capillary zone electropho- variants can be missed by these methodologies and resis (CZE) revealed 89.4% Hb A, 2.5% Hb A2, and an require additional testing, including molecular abnormal Hb peak (5.3%) at the junction of zone 11 analysis [3]. Here we report a case of a rare alpha- and zone 12 (Figure 1). The possibility of degraded Hb chain Hb variant identified by DNA analysis. due to inadequate handling of the specimen was the ini- tial impression, and a repeat Hb electrophoresis was rec- ommended. Repeat CZE confirmed the abnormal Hb Case report peak (5.5%) at the same position (junction of zone 11 and zone 12). Concurrent high pressure liquid chroma- A 47-year-old man presented with a clinical history sig- tography (HPLC) showed an unknown Hb (6.5%) with nificant for secondary polycythemia. A complete blood a retention time of 1.52 minutes in the P 3 peak (Figure count and hemoglobin analysis were performed. 2). Laboratory data revealed Hb of 16.9 g/dL, a hematocrit of 52.8%, a mean corpuscular volume of 84.4 fL, and DNA sequencing of the whole blood EDTA sample was performed. Alpha globin gene sequencing demonstrated Address correspondence to Amer Wahed, MD., The University of Texas Health Science Center at Houston-McGovern Medical School, one copy of an alpha globin gene variant, Hb Wayne, in 6431 Fannin Street, Houston, TX, 77030 USA; phone: 713 500 5330; the HBA2 gene. No mutations were detected in the e mail: [email protected] HBA1 gene and beta globin gene. 0091-7370/17/0100-096. © 2017 by the Association of Clinical Scientists, Inc. Hemoglobin Wayne 97 Discussion Hb Wayne is a rare alpha chain Hb variant caused by a frameshift mutation in the HBA2 gene. It was first described in 1976 in a 7-year-old boy with Fanconi’s anemia [4]. It exists in two forms, Hb Wayne I (asparagine as residue 139) and Hb Wayne II (aspartic acid as residue 139) [5]. There is limited literature available about this rare variant [4-8], so the prevalence of the Hb Wayne trait is unknown. Carriers of single alpha gene mutations for Hb Wayne are clinically normal with unremarkable he- matological indices. Hb Wayne has high oxygen af- finity with a reduced Bohr effect [5], but carriers of one affected alpha globin gene are clinically normal with no secondary polycythemia due to low levels of Hb Wayne. Since the patient is not homozygous for Hb Wayne, which is associated with secondary polycythemia, the laboratory diagnosis in this case is critical in ruling out hemoglobinopathy as the Figure 1. Capillary zone electrophoresis showing the pres- etiology of his polycythemia. ence of likely Hb Wayne (5.3%) at the junction of zone 11 and zone 12. Even though it is a clinically silent variant, studies have shown that Hb Wayne can confound HbA1c measurements through various mechanisms, espe- cially in HPLC [9,10]. Of note, the patient in this case report had no history of diabetes. Studies have shown that the presence of Hb variants should be considered as a differential when there are discrep- ancies in the HbA1c and blood glucose levels, par- ticularly in asymptomatic patients [9-12]. In conclusion, Hb variants are difficult to diagnose based on clinical presentation and routine Hb anal- ysis alone. The rationale of this case report is not only to describe this rare entity and its implications in HbA1c measurement, but also to highlight the role of secondary molecular analysis to correctly di- agnose hemoglobinopathies. References 1. Greene DN, Vaughn CP, Crews BO, Agarwal AM.Advances in detection of hemoglobinopathies. ClinChimActa. 2015 Jan Figure 2. Bio-Rad Variant V-II HPLC showing 6.5% of 15;439:50-7. unknown Hb with a retention time of 1.52 minutes in the 2. Costa D, CapuanO M, Sommese L, Napoli C. Impact of epi- P3peak. genetic mechanisms on therapeutic approaches of hemoglobin- opathies. Blood Cells Mol Dis. 2015 Aug;55(2):95-100. 98 Annals of Clinical & Laboratory Science, vol. 47, no. 1, 2017 3. Honarpisheh H, Staba Hogan MJ, Rinder HM, Siddon AJ. 8. Reynolds TM, Harvey TC, Green BN, Smith A, Hartland AJ. Hemoglobinopathy Screening in a 15-Year-old Patient With Hemoglobin Wayne in a British family: identification by elec- Anemia.JPediatr Hematol Oncol. 2015 Aug;37(6):472-3. trospray ionization/mass spectrometry. Clin Chem. 2002 4. Seid-Akhavan M, Winter WP, Abramson RK, Rucknagel DL. Dec;48(12):2261-3. Hemoglobin Wayne: a frameshift mutation detected in human 9. Rodríguez-Capote K, Estey MP, Barakauskas VE, Burton T, hemoglobin alpha chains. Proc Natl Acad SciUSA. 1976 Holmes D, Krause R, Higgins TN. Identification of Hb Wayne Mar;73(3):882-6. and its effects on HbA1c measurements by 5 methods. Clin 5. Moo-Penn WF, Jue DL, Johnson MH, McDonald MJ, Turci Biochem. 2015 Nov;48(16-17):1144-50. SM, Shih TB, Jones RT, Therrell BL Jr, Arnone A. Structural 10. Chen J, Diesburg-Stanwood A, Bodor G, Rasouli N. Led and functional studies of hemoglobin Wayne: an elongated al- Astray by Hemoglobin A1c: A Case of Misdiagnosis of Diabetes pha-chain variant. J Mol Biol. 1984 Dec 25;180(4):1119-40. by Falsely Elevated Hemoglobin A1c. J Investig Med High 6. Huisman TH, Headlee MG, Wilson JB, Lam H, Johnson SE, Impact Case Rep. 2016 Jan 28;4(1):2324709616628549. Webber BB. Hb Wayne, the frameshift variant with extended 11. Brunel V, Lahary A, Chagraoui A, Thuillez C. Hemoglobin alpha chains observed in a Caucasian family from Alabama. J-Baltimore can be detected by HbA1c electropherogram but Hemoglobin. 1984;8(1):1-15. with underestimated HbA1c value. Biochem Med (Zagreb). 7. Salkie ML, Higgins T, Morrison DM, Wilson JB, Gu LH, 2016;26(2):240-2. Cürük MA, Baysal E, Huisman TH.A Canadian family with 12. Saw S, Loh TP, Yin C, Sethi SK. Identification of hemoglobin Hb Wayne; characterization by HPLC and DNA sequencing. variants in samples received for glycated hemoglobin testing. Hemoglobin. 1992;16(6):515-9. Clin Chim Acta. 2013 Jan 16;415:173-5..
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