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LETTER TO EDITOR  
Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 270-271
Falsely low HbA1c value due to a rare hemoglobin variant (HEMOGLOBIN J-MEERUT) - A family study


Department of Pathology, Dr. RML Hospital and PGIMER, New Delhi, India

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Date of Web Publication3-Jul-2012
 

How to cite this article:
Sharma A, Marwah S, Buxi G, Yadav RB. Falsely low HbA1c value due to a rare hemoglobin variant (HEMOGLOBIN J-MEERUT) - A family study. Indian J Pathol Microbiol 2012;55:270-1

How to cite this URL:
Sharma A, Marwah S, Buxi G, Yadav RB. Falsely low HbA1c value due to a rare hemoglobin variant (HEMOGLOBIN J-MEERUT) - A family study. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Feb 25];55:270-1. Available from: http://www.ijpmonline.org/text.asp?2012/55/2/270/97912


Sir,

Glycosylated hemoglobin (HbA1c) is routinely used to monitor long term glycemic control in diabetic patients. [1] We report a family of rare and abnormal hemoglobin (Hemoglobin J-Meerut) showing falsely low level of HbA1c, not corresponding to their respective fasting plasma glucose levels.

A 23-year-old pregnant female came for thalassemia screening as a part of routine antenatal check-up. Her hemogram and RBC indices were normal. High Performance Liquid Chromatography (HPLC) variant analysis on beta-thal program showed an unknown hemoglobin peak of 19% between P3 and A0 window at the retention time of 1.90 minutes [Figure 1]. HPLC analysis of her family showed the presence of same abnormal hemoglobin peak in her mother and two younger siblings as seen in the patient herself [Figure 1]. The mean percentage of this abnormal hemoglobin variant in these four family members was 19.025% eluted at a retention time of 1.87-1.90 minutes [Table 1]. A diagnosis of HbJ-Meerut was made by matching the retention time in the catalog provided by BioRad Variant system.
Figure 1: HPLC variant analysis of all the four family members showing abnormal hemoglobin peak of Hemoglobin J-Meerut: (a) Patient; (b) Patient's mother; (c) Patient's sister; and (d) Patient's brother

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Table 1: Hemogram and HPLC fi ndings of the four members of this family showing abnormal hemoglobin variant (Hemoglobin J-Meerut)

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An attempt was made to find out correlation between glycosylated hemoglobin (HbA1c) and the blood sugar levels in all these four family members of HbJ-Meerut. Being aware of the fact that the patient's mother was a recently and incidentally diagnosed case of diabetes mellitus, her fasting blood sugar levels and HbA1c were performed and correlated. Her fasting blood sugar level obtained was 240 mg/dl corresponding to the value >8-9% of HbA1c. [1] Surprisingly, falsely low value of 6.9% was obtained [Figure 2] which corresponds to an average blood glucose level of approximately 170 mg/dl. [1] Similarly, the remaining three family members with HbJ-Meerut also showed falsely low values of HbA1c as shown in [Table 2]. On follow-up, the family showed persistently falsely low values of HbA1c not corresponding to their respective fasting plasma glucose levels.
Figure 2: Chromatograms showing HbA1c values all the four family members showing abnormal hemoglobin variant (Hemoglobin J-Meerut): (a) Patient's mother; (b) Patient; (c) Patient's sister; and (d) Patient's brother

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Table 2: Falsely low value of HbA1c in all the four family members of HbJ-Meerut

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Hemoglobin J is a heterogeneous group of fast moving hemoglobins (FMHs), resulting from substitution of a negatively charged amino acid residue in either α, β, or γ globin chains. [2] Hemoglobin J-Meerut can be differentiated and identified solely on its retention time. [2] Blackwell et al. first reported this Hb variant in two sisters from Meerut in India. [3] Worldwide, very few case reports of this hemoglobin variant (Hb-J Meerut) are available. [2]

Our case is the first family of HbJ-Meerut which has come to our department in the past six years depicting its rarity (1 in approx. 4000 cases). Abnormal hemoglobins which produce no hematological symptoms are rarely detected. [4] Srinivas et al. documented that majority of FMHs of J-family are clinically silent and therefore are detected accidentally during family or antenatal screening as seen our case. [2]

This HbJ-Meerut family showed the characteristic finding of falsely lower levels of HbA1c than expected from their plasma glucose levels. A single case report of a diabetic case with Hemoglobin J-Meerut and low HbA1c levels has been reported in the literature. [4]

As HbA1c is based on Hb, both quantitative and qualitative variations in Hb can affect the HbA1c value. [5] If the Hb substitution causes a net change in charge of the Hb (as with Hb variants S, C, D, and G), or if Hb variants cannot be separated from HbA/HbA1c will produce spuriously increased or decreased results by HPLC. [5] Co-elution of the Hb variant with HbA, with resolution of the glycated Hb variant from HbA1c, may under-estimate the HbA1c results as seen in our case.

Thus, knowledge and awareness of Hb-variants affecting HbA1c measurements is essential in order to avoid mismanagement of diabetic patients.

 
   References Top

1.American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes care 2003;26 Suppl 1:S33-50.  Back to cited text no. 1
    
2.Srinivas U, Mahapatra M, Pati HP. Hemoglobin J-Meerut, A fast moving hemoglobin- A study of seven cases from India and a review of literature. Am J Hematol 2007;82:666-7.  Back to cited text no. 2
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3.Blackwell RQ, Wong HB, Wang CL, Weng MI, Liu CS. Hemoglobin J Meerut: α120 Ala leads to Glu. Biochim Biophys Acta 1974;351:7-12.  Back to cited text no. 3
[PUBMED]    
4.Yagame M, Jinde K, Suzuki D, Saotome N, Takano H, Tanabe R, et al. A diabetic case with Hemoglobin J-Meerut and low HbA1c levels. Intern Med 1997;36:351-6.  Back to cited text no. 4
    
5.Little RR, Roberts WL. A review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol 2009;3:446-51.  Back to cited text no. 5
    

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Correspondence Address:
Anjali Sharma
Department of Pathology, Dr. Ram Manohar Lohia Hospital and PGIMER, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.97912

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    Figures

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    Tables

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