Korean J Lab Med.  2009 Dec;29(6):536-540. 10.3343/kjlm.2009.29.6.536.

Hemoglobin Yamagata: Hemoglobin Variant Detected by HbA1c Test

• Jung CL
• Kwon KJ
• Hong KS
• Sung YA
• Lee ST
• Ki CS
• Lee MA
• Chung WS

• KMID: 1781607
• DOI: http://doi.org/10.3343/kjlm.2009.29.6.536

Abstract

Hemoglobin (Hb) Yamagata is a rare Hb variant, which has been reported only twice-one case each in Japan and Korea. This variant arises from a Lys --> Asn substitution due to a mutation of AAA to AAC or AAT at codon 133 of the beta-globin gene. This study reports the third case of a patient detected with Hb Yamagata [HBB: c.399A>T; p.Lys133Asn] and discusses the effect of this variant on HbA1c measurement. This variant was detected in a 70-yr-old Korean man with diabetes mellitus during a routine follow-up. The HbA1c concentration determined using Variant ll Turbo (Bio-Rad, USA) was abnormally high at 47.9%. It was impossible to measure the HbA1c level accurately using Variant ll Thalassemia Mode (Bio-Rad, USA). However, the HbA1c levels analyzed by HLC-723 G7 (Tosoh, Japan), Cobas Integra (Roche, Switzerland) and NycoCard (Axis-Shield, Norway) were 5.0%, 8.0%, and 7.9%, respectively. This study shows that Hb Yamagata interferes with the accurate measurement of HbA1c levels in a diabetic patient. Taking these findings into consideration, we think that an immunoassay or affinity chromatography can be used as an alternate method for measuring the HbA1c level in a patient with this variant. In conclusion, a patient can be inferred to have an Hb variant if the HbA1c concentration is abnormally high or low or if there is a discrepancy between the results obtained using different methods, and if the clinical status of the patient suggests the presence of abnormal Hb. Subsequently, the HbA1c values can be determined by methods based on different principles.

Keyword

Hb Yamagata; Hb variant; HbA1c; HPLC

MeSH Terms

Aged
Amino Acid Substitution
Diabetes Mellitus/diagnosis
Electrophoresis, Capillary
Hemoglobin A, Glycosylated/*analysis
Hemoglobins, Abnormal/*analysis
Humans
Male
Reagent Kits, Diagnostic
Sequence Analysis, DNA
beta-Globins/genetics

Figure

• 

  Fig. 1. Chromatograms for HbA1c level of the patient with Hb Yamagata obtained using (A) Variant II Turbo (Bio-Rad, USA), (B) Variant II Thalassemia mode (Bio-Rad, USA), and (C) HLC-723 G7 (Tosoh Corporation, Japan). The arrows indicate the retention time of Hb Yamagata.

• 

  Fig. 2. Globin gene analysis: Hb Yamagata (HBB c.399A>T; p.Lys133Asn) (arrow). The DNA sequence analysis showed the presence of Hb Yamagata, in which the Lys→Asn substitution was due to a mutation of AAA to AAT at codon 133 of the beta-globin gene.

• 

  Fig. 3. Electrophoregrams of Hb Yamagata as obtained by the Sebia capillary EP system. The arrow indicates Hb Yamagata. The fractions of Hb Yamagata, HbA, and HbA2 were 40.9%, 54.4%, and 3.0%, respectively.

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