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Clinical Chemistry 46: 139-a-140-a, 2000;
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(Clinical Chemistry. 2000;46:139-140.)
© 2000 American Association for Clinical Chemistry, Inc.

Letters

Elution of Hemoglobin {alpha}Montgomery2ßS2 Hybrid Tetramers by the Variant Apparatus

Jonathan S. Kraussa,1

a Address correspondence to this author at: BIH-222B, MCG, Pathology, 1120 15th St., Augusta GA 30912-3620. Fax 706-721-7837; e-mail jkrauss{at}mail.mcg.edu

Keith Bures1
Elizabeth Kenimer1

1 Department of Pathology, Section of Clinical Pathology, Medical College of Georgia, Augusta, GA 30912


To the Editor:

Hemoglobin (Hb) Montgomery ({alpha}48 Leu->Arg) is an uncommon variant first reported in 1975 (1). We report here a case of the association of homozygous HbS (ß6 Glu->Val) with this variant identified by the late Dr. T.H.J. Huisman in an 8-year-old black girl with a life-long sickling disorder.

We quantified Hb fractions by cation-exchange HPLC with the VariantTM Hemoglobin Testing System Beta-Thalassemia Short Program (Bio-Rad Diagnostics) (2)(3). The complete blood count was determined by a Beckman-Coulter STKSTM. Alkaline Hb electrophoresis was performed on cellulose acetate (Helena Laboratories). Solubility testing was done with phosphate-buffered saline using SickleScreenTM (Pacific Hemostasis). The Hb was 88 g/L [reference interval (RI), 110–160 g/L], mean cell volume was 83.1 fL (RI, 80–98 fL), and the red cell distribution width was 19.5% (RI, 11.5–18.0%). HbF, HbA2, HbS, and "HbC" were 8.9%, 3.8%, 67.7%, and 15.8%, respectively, by HPLC (Fig. 1 ). The blood sample was solubility positive. Alkaline Hb electrophoresis had an "HbSCF" pattern with an abnormal HbA2 band.



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  		Figure 1. HPLC elution pattern of a whole-blood hemolysate.

F, HbF elution peak; A2, HbA2; S, HbS; M-S, Hb {alpha}Montgomery2ßS2 hybrid tetramers. A0 may reflect glycated HbS components that elute with HbA0.

Although Hb Montgomery is not rare in African Americans (4), it is less common than HbG-Philadelphia ({alpha}68 Asn->Lys); hence, the combination of homozygous HbS and Hb Montgomery in this patient (A. Kutlar, personal communication) is very uncommon, although an accurate prevalence estimate of this condition is unknown to us. The lack of HbA by both HPLC and alkaline electrophoresis confirms homozygosity for HbS; therefore, the HbC window by HPLC and the band on cellulose acetate are {alpha}Montgomery2ßS2 hybrid tetramers. The elution of these tetramers in the HbC window on the Variant has not been reported. This window cannot contain Hb Montgomery ({alpha}Montgomery2ß2) because only ßS chains were synthesized. Hb Montgomery is a stable variant of the {alpha}2-globin gene ({alpha}x{alpha}/{alpha}{alpha}) (5); the relatively high concentration of hybrid tetramers (15.8%; {alpha}Montgomery2ßS2) here reflects the high degree of {alpha}-chain variant stability and its affinity for the ßS chains (5)(6). In alkaline Hb electrophoresis, the {alpha}Montgomery2ßS2 hybrid tetramers behave similarly to {alpha}G-Philadelphia2ßS2 hybrid tetramers, which also migrate to the HbC position (6).


References

  1. Brimhall B, Jones RT, Schneider RG, Hosty TS, Tomlin G, Atkins R. Hemoglobin Alabama [ß39(C5)Gln->Lys] and hemoglobin Montgomery [{alpha}48(CD6)Leu->Arg]. Biochim Biophys Acta 1975;379:28-32. [Medline] [Order article via Infotrieve]
  2. Suh DD, Krauss JS, Bures K. Influence of hemoglobin S adducts on hemoglobin A2 quantification by HPLC. Clin Chem 1996;42:1113-1114. [Free Full Text]
  3. Thomas S. Sample dilution to resolve mistaken identification of haemoglobin D as haemoglobin E using the VariantTM automated system. J Clin Pathol 1998;51:253-254. [Abstract]
  4. Zeng Y-T, Huang S-Z, Dong Z-Y, Lam H, Wilson JB, Huisman THJ. Hemoglobin Montgomery ({alpha}248Leu->Arg ß2) in a Chinese family. Hemoglobin 1982;6:213-215. [Web of Science][Medline] [Order article via Infotrieve]
  5. Molchanova TP, Pobedimskaya DD, Huisman THJ. The differences in quantities of {alpha}2- and {alpha}1-globin gene variants in heterozygotes. Br J Haematol 1994;88:300-306. [Web of Science][Medline] [Order article via Infotrieve]
  6. Felice A, Abraham EC, Miller A, Cope N, Gravely M, Huisman THJ. Post-translational control of human hemoglobin synthesis; the number of {alpha} chain genes and the synthesis of HbS. Brewer GJ eds. The red cell 1978:131-153 AR Liss New York. .



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Home page
 Clin. Chem.Home page
G. M. Clarke and T. N. Higgins
Laboratory Investigation of Hemoglobinopathies and Thalassemias: Review and Update
Clin. Chem., August 1, 2000; 46(8): 1284 - 1290.
[Abstract] [Full Text] [PDF]

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