Rare hemoglobin variant Hb I Philadelphia in North Indian family

Abstract

Dear Editor, Hemoglobinopathies are important inherited disorders that are highly prevalent in India constituting a significant public heath problem. The three most predominant clinically relevant abnormal hemoglobins are Hb S, Hb E, and Hb D with the cumulative gene frequency 5.35% in India [1]. Apart from these, Hb H, J, K, L, M, Q, Koya-Dora, Chandigarh are other variants detected so far in India [2]. This paper reports a rare variant of alpha globin chain Hb I Philadelphia present in a Hindu family. Hb I Philadelphia [α 16 (A14) Lys-Glu] is a fast alpha globin chain variant resulting from point mutation in codon 16 of α1 globin gene AAG-GAG that leads to a substitution of lysine by glutamic acid. It has considerably lower isoelectric point than normal hemoglobin (Hb A) and moves ahead of Hb A at alkaline pH similar to the Hb H migration, while at acidic pH, it migrates with Hb A [3]. The concentration of mutant protein is 24–28% in heterozygotes with normal stability. It is clinically asymptomatic in carriers [4]. Rucknagel et al. described Hb I Philadelphia for the first time in 1955 in an Afro-American family [3]. After that, it was identified in different ethnic groups with low frequency viz Africans, American, Caucasians, and Asians. This is the first report from India, which indicates the presence of Hb I Philadelphia in an Indian subject and its association with β thalassemia. Several fast hemoglobin variants can produce varied interference in cation exchange chromatography of Hb A1c, which require careful interpretation [5]. Krauss and Khankhanian demonstrated the effectiveness of highperformance liquid chromatography (HPLC) in distinguishing Hb A1c and Hb I Philadelphia [6]. A 48-year-old male patient visited the Department of Endocrinology with some specific problems. Co-morbids include cholelithiasis. Here, he was prediagnosed with diabetes mellitus type II and his initial Hb A1c (performed on Bio-Rad D10, Hemoglobin A1c Program. Bio-Rad Laboratories, Hercules, CA, USA) was evaluated as 12.2% (reference range for non-diabetic normal population 4–6%). The pre-breakfast glucose levels and random glucose levels were 129 and 235 mg/dl, respectively (reference range for fasting and random plasma glucose levels defined by WHO are 126 and 200 mg/dl, respectively). The measurement of Hb A1c and blood glucose levels were done at 5–6 months interval. As his HbA1c chromatogram showed abnormal unexplained peak (Fig. 1), he was referred to the Department of Genetics for the possible exclusion of hemoglobinopathy. Here, his complete blood counts were analyzed on an automated cell counter (Sysmex Kx-21, Japan). His Hb, MCV, and MCH were 12.8 g/dL, 80.0 fL, and 28.0 pg, respectively. Peripheral smear was not reviewed. Hemoglobin electrophoresis on cellulose acetate at pH 8.6 showed an abnormal fast-moving hemoglobin band. The sample was reanalyzed on HPLC (Bio-Rad Variant β Thalassemia short program-Bio-Rad Laboratories, Hercules, CA,USA) Ann Hematol (2009) 88:927–929 DOI 10.1007/s00277-009-0710-1