HB UBE-2 variant hemoglobin case detected during HBA1C measurement

Yıl 2021, Cilt: 46 Sayı: 2, 866 - 868, 30.06.2021

Evin Kocatürk , Zeynep Kusku Kiraz , Şükrü Demir Oğuz Çilingir , Hava Üsküdar Teke , İ. Özkan Alataş

Öz

Hemoglobin A1c is used in the diagnosis and the management of Diabetes Mellitus. The accuracy of hemoglobin A1c measurements may be affected by various factors and the most common interferences are variant hemoglobins. During hemoglobin A1c measurement of a 56-year-old female patient with Type 2 Diabetes Mellitus, an abnormal peak was detected in the chromatogram by high performance liquid chromatography and an inconsistency was determined between the serum glucose and the hemoglobin A1c value. Patient’s hemoglobin A, hemoglobin A2, hemoglobin F and variant hemoglobin were detected as 73.3, 2, 0.3 and 24.4% respectively in the capillary electrophoresis. Hemoglobin value of patient was 13.5 g / dL, red blood cell 4.40x106 / µL, mean cell volume 89.8 fL, mean corpuscular hemoglobin 30.7 pg and the blood smear examination was evaluated as normal, however, heterozygote (αube-2α/αα) NM_000558.4 c.205A>G p.(Asn69Asp) variation was detected in hemoglobin A1 gene by whole exome sequencing and this variation is defined as hemoglobin Ube-2. It should be known that variant hemoglobin may affect to hemoglobin A1c measurements and especially when the results are incompatible with patient’s clinical status, this effect should be considered.

Anahtar Kelimeler

Hemoglobin A1c, Variant hemoglobin, Hemoglobin Ube-2, Interference

HBA1C ölçümü sırasında saptanan HB UBE-2 varyant hemoglobin olgusu

Öz

Hemoglobin A1c, Diabetes Mellitus'un tanısında ve hasta yönetiminde kullanılır. Hemoglobin A1c ölçümlerinin doğruluğu çeşitli faktörlerden etkilenebilir ve en çok karşılaşılan interferans varyant hemoglobinlerdir. 56 yaşında Tip 2 Diabetes Mellitus’u olan kadın hastanın hemoglobin A1c ölçümü sırasında, yüksek performanslı likit kromatografi ile kromatogramda anormal bir pik tespit edildi ve serum glukozu ile hemoglobin A1c değeri arasında tutarsızlık tespit edildi. Kapiller elektroforezde hastanın hemoglobin A, hemoglobin A2, hemoglobin F ve varyant hemoglobini sırasıyla% 73.3, 2, 0.3 ve 24.4 olarak tespit edildi. Hastanın hemoglobin değeri 13.5 g / dL, eritrosit sayısı 4.40x106 / µL, ortalama eritrosit hacmi 89.8 fL, ortalama korpüsküler hemoglobin 30.7 pg idi ve periferik yayma incelemesi normal olarak değerlendirildi, ancak heterozigot (ααube-2α / αα) NM_000558 .4 c.205A> G p. (Asn69Asp) varyasyonu hemoglobin A1 geninde tam ekzon sekanslama yöntemi ile tespit edilmiş ve bu varyasyon hemoglobin Ube-2 olarak tanımlanmıştır. Varyant hemoglobinin hemoglobin A1c ölçümlerini etkileyebileceği bilinmeli ve özellikle sonuçlar hastanın klinik durumu ile uyumsuz olduğunda bu etki dikkate alınmalıdır.

Anahtar Kelimeler

Hemoglobin A1c, Varyant hemoglobin, Hemoglobin Ube-2, İnterferans

Kaynakça

• Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem. 47 (2001) 153-63.
• Weykamp C. HbA1c: A Review of Analytical and Clinical Aspects. Ann Lab Med. 33 (2013) 393-400.
• Thevarajah TM, Nani N, Chew YY. Performance evaluation of the Arkray Adams HA-8160 HbA1c analyser. Malays J Pathol. 30 (2008) 81-6.
• Little RR and Rohlfing CL. The long and winding road to optimal HbA1c measurement. Clin Chim Acta. 418 (2013) 63-71.
• ClinVar Genomic variation as it relates to human health NM_000558.5(HBA1):c.205A>G (p.Asn69Asp) https://www.ncbi.nlm.nih.gov/clinvar/variation/15831/ (Accessed 10.05.2020).
• Arneson W, Brickell J. Diabetes and other carbohydrate disorders. In: Brickell J, Freeman V, Arneson W. Clinical Chemistry, A Laboratory Perspective. 2007. p. 147-78.
• The Society of Endocrinology and Metabolism of Turkey Diabetes Mellitus Working Group. Diagnosis, classification and screening in glycemic disorders. Clinical Practice Guideline for Diagnosis, Treatment and Follow-up of Diabetes Mellitus and Its Complications. 12th Ed. 2019. p. 15-32.
• WHO, Use of glycated hemoglobin (HbA1c) in the diagnosis of diabetes mellitus. http://www.who.int/diabetes/publications/report-hba1c_2011.pdf (Accessed 05.05.2020).
• American Diabetes Association. Standards of medical care in diabetes – 2010. Diabetes Care. 33 (2010) 11–61.
• National Glycohemoglobin Standardization Program (NGSP), HbA1c assay interferences. http://www.ngsp.org/interf.asp (Accessed 20.05.2020).
• Yamane Y, Tsumori1 M, Ishibashi M, Koga M. A case of variant hemoglobin (Hb Agenogi) with type 2 diabetes mellitus showed high HbA1c levels measured by immunoassay due to enhanced antigenicity. Diabetology International. 10 (2019) 138–42.
• Huang Y , Lin M, Lin CP, Wu JR, Zheng LH, Yang LY. Molecular Characteristics of Three Hemoglobin Variants Observed in a Chinese Population: Hb Ube-1 [β98 (FG5) Val→Met], Hb Ube 2 [α68 (E17) Asn→Asp] and Hb Ube 4 [α116 (GH4) Glu→Ala] Mol Med Rep 2011;4(4):681-5.
• Miyaji T, Iuchi I, Yamamoto K, Ohba Y, Shibata S. Amino Acid Substitution of Hemoglobin Ube 2 (alpha-2 68asp beta-2): An Example of Successful Application of Partial Hydrolysis of Peptide with 5 Per Cent Acetic Acid. Clin Chim Acta. 1967 16(3):347-52.
• Hamaguchi K, Harano K, Harano T, Abe N, Sakata T. Hb Ube-2 in a Diabetic Case with an Abnormally Low HbAlc Value. Intern Med 1999;38(10):800-3.
• Xu A, Chen W, Xia Y, Zhou Y, Ji L. Effects of Common Hemoglobin Variants on HbA1c Measurements in China: Results for α- And β-Globin Variants Measured by Six Methods. Clin Chem Lab Med 2018;56(8):1353-1361. https://doi.org: 10.1515/cclm-2017-1211.
• Otabe S, Nakayama H, Ohki T, Soejima E, Tajiri Y, Yamada K. Haemoglobin Variants May Cause Significant Differences in Haemoglobin A1c as Measured by High-Performance Liquid Chromatography and Enzymatic Methods in Diabetic Patients: A Cross-Sectional Study. Ann Clin Biochem 2017;54(4):432-7.
• Bilginer A, Lehmann H, Arcasoy A. Hemoglobin Ube-2 (alpha 68 Asn----Asp) observed in a Turkish family. Hemoglobin. 1984;8(2):189-91.
• Bircan I, Sişli S, Güven A, Cali S, Yeğin O, Ertuğ H, Güven AG, Akar N. Hemoglobinopathies in the district of Antalya, Turkey. Pediatr Hematol Oncol. 1993;10(3):289-91.