eI o nII rioui Columbia Hemoglobin CHarlem (Georgetown) trait in British -

Brian D. Jollymore, MD; George R. Gray, MD, FRCPC; Sheldon C. Naiman, MD, FRCPC H

emoglobin (Hb) S is the most important phoresis

on

hemoglobin variant in black people. About addition

to Hb A, a band with the electrophoretic

8% of black Americans have sickle cell trait (heterozygous state); less than 1% have sickle cell anemia (homozygous state).' We report a case of Hb CHarlem (Georgetown) trait. Hb CHarlem (Georgetown) is a variant of Hb S with a mobility similar to that of Hb C at alkaline pH; however, the erythrocytes sickle in vitro like those containing Hb S.2,3

citrate

agar at

pH 6.04 showed, in

mobility of Hb S (Fig. 2). Sickling was demonstrated with the Chembio Diagnostic Systems Sickle STAT test (Yaphank, New York)5 and the 2% sodium metabisulfite test.4 The results were consistent with the diagnosis of Hb CHarlem (Georgetown) trait.

Comments

Case report

Pierce, Rath and McCoy3 reported the first case of Hb CHarlem (Georgetown) trait. The erythrocytes sickled A 38-year-old gravida 3, para 1 asymptomatic on deoxygenation, yet the Hb had the electrophoretic black woman had a routine blood count done at 20 mobility of Hb C. It was not until several years later weeks' gestation. Her Hb concentration was 124 g/L; that the structure of the Hb variant was identified. the morphologic features of the erythrocytes were In 1967 Bookchin, Nagel and Ranney2 described an normal. She had a family history of sickle cell apparently new variant, which they called Hb CHarlem. anemia, and as a child she had been investigated They found that the variant had a double amino twice for the condition, with negative results. Hb electrophoresis on cellulose acetate at pH 8.64 showed, in addition to Hb A, a band with the electrophoretic mobility of Hb C (Fig. 1). Electro-

Normal

Patient

FASC

Normal

Patient

A/S

A/S

AFSC

A/C

AF S C Fig. 1: Results of hemoglobin (Hb) electrophoresis on cellulose acetate at pH 8.6, showing normal Hb A band and abnormal band with mobility of Hb C.

F AS C Fig. 2: Results of Hb electrophoresis on cellulose acetate at pH 6.0, showing normal Hb A band and abnormal band with mobility of Hb S.

Dr. Jollymore is a resident in general pathology, University of British Columbia, Vancouver, Dr. Gray is head, Division of Hematopathology, Vancouver General Hospital, and associate professor ofpathology, University ofBritish Columbia, and Dr. Naiman is director, Hematology Laboratory, Vancouver General Hospital, and clinical professor ofpathology and medicine, University of British Columbia.

Reprint requests to: Dr. George R. Gray, Division ofHematopathology, Vancouver General Hospital, 855 W 12th Ave., Vancouver, BC V5Z IM9 CAN MED ASSOC J 1990; 142 (6)

99

acid substitution of the (3 chain. Its structure was a2,(,26 Ciu-Val. 73 Asp-Asn. It was subsequently discovered that the two Hb variants were identical. It is likely that the patient we have described had the Hb CHar,em (Georgetown) trait, although other rare sickling hemoglobins with a double mutation have been described.6 The 26 GIu-Val mutation is identical to the mutation found in Hb S. The ,B273 Asp-Asn mutation is identical to the mutation found in HbKorle Bu- It has been postulated that this double (3 gene mutation may have arisen from a homologous crossing over of the individual (3 gene mutations.7 Alternatively, it could be a second mutation in a patient with Hb S. It is the double mutation that gives the Hb an electrophoretic mobility (at pH 8.6) similar to that of Hb C. As the black population increases in Canada, so does the potential for finding Hb S and Hb CHarlemr(Georgetown), Therefore, the ability to screen reliably for sickle Hb variants is important. Minimal investigation should include Hb electrophoresis at pH 8.6 and a sickle cell test. If the pattern suggests heterozygosity for Hb C and the sickle cell test yields positive results, Hb electrophoresis at pH 6.0 should be performed. If such tests were not performed sickle Hb variants other than Hb S would not be identified. The exact nature of the investigation of sickle cell anemia that had been done when the patient was a child is not known. However, it is presumed that Hb A and C trait had been diagnosed and that further tests had not been done. We thank Dr. Anthony H. Robinson for referring the patient and Mrs. Rae Jahrig for her help in preparing the

manuscript.

References 1. Myerson RM, Harrison E, Lohmuller HW: Incidence and significance of abnormal hemoglobins: report of a series of 1,000 hospitalized Negro veterans. Am J Med 1959; 26: 543546 2. Bookchin RM, Nagel RL, Ranney HM: Structure and properties of hemoglobin CHarlem, a human hemoglobin variant with amino acid substitutions in two residues of the beta-polypeptide chain. JBiol Chem 1967; 242: 248-255 3. Pierce LE, Rath LE, McCoy K: A new hemoglobin variant with sickling properties. N Engl J Med 1963; 268: 862-866 4. Weatherall DJ: The thalassemias. In Methods of Hematology, vol 6, Churchill, New York, 1983: 31-53 5. Greenburg MS, Harvey HA, Morgan C: A simple and inexpensive screening test for sickle cell hemoglobin. N Engl J Med 1972; 286: 1143-1144 6. Langdown JV, Williamson D, Knight CB et al: A new doubly substituted sickling haemoglobin: HbS-Oman. Br J Haematol 1989; 71: 443-444 7. Konotey-Ahulu FID, Gallo E, Lehmann H et al: HaemoglobinKore B. (beta 73 aspartic acid replaced by asparagine) showing one of the two amino acid substitutions of haemoglobin CHarlem. JMed Genet 1968; 5: 107-111 600

CAN MED ASSOC J 1990; 142 (6)

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Hemoglobin CHarlem (Georgetown) trait in British Columbia.

eI o nII rioui Columbia Hemoglobin CHarlem (Georgetown) trait in British - Brian D. Jollymore, MD; George R. Gray, MD, FRCPC; Sheldon C. Naiman, MD,...
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