International Journal of Hematology

, Volume 80, Issue 5, pp 410–415 | Cite as

Hb Bristol-Alesha Presenting Thalassemia-Type Hyperunstable Hemoglobinopathy

  • Gen Kano
  • Akira Morimoto
  • Shigeyoshi Hibi
  • Chika Tokuda
  • Shinjiro Todo
  • Tohru Sugimoto
  • Teruo Harano
  • Ayako Miyazaki
  • Akira Shimizu
  • Shinsaku Imashuku
Article

Abstract

Hemoglobin (Hb) Bristol-Alesha is caused by a GTG→ ATG mutation at codon 67 in the Hb ß chain, resulting in abnormal ß globin chains with mutated molecules from normal ß67 valine (Val) to ß67 methionine (Met) or ß67 aspartate (Asp). We describe a Japanese child with this rare hemoglobinopathy and a very unstable Hb molecule phenotype. The diagnosis of hemolytic anemia was made when the patient was 6 months of age. Development of marked splenomegaly necessitated red blood cell transfusions twice a month. After splenectomy when the patient was 4 years of age, laboratory findings of hemolytic anemia became more prominent. Specific abnormal Hb molecules initially were not detected, and the α/ß globin synthesis ratio was abnormal at 2.22. After splenectomy, we identified the presence of abnormal ß-globin chains with a ß67Val:ß67Met:ß67 Asp molecule ratio of 74:11:15. We speculate that the high fraction of the ß67Met molecule in this patient, compared with that in previously reported cases, caused extreme Hb instability, which resulted in thalassemic hyperunstable hemoglobinopathy and very severe clinical findings.

Key words

Hb Bristol Hb Bristol-Alesha Posttranslational modification Hyperunstable hemoglobin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hörlein H, Weber G. Über chromische familiäre Methamoglo- binämie und eine neue Modifikation des methämoglobins. Dtch Med Wochenschr. 1948;73:4.Google Scholar
  2. 2.
    Pauling L. Sickle cell anemia: a molecular disease. Science. 1949; 110:543.CrossRefPubMedGoogle Scholar
  3. 3.
    Huisman TH, Carver MF, Efremov GD. A Syllabus of Human Hemoglobin Variants. 2nd ed. Augusta, GA: Sickle Cell Anemia Foundation; 1998.Google Scholar
  4. 4.
    Steadman JH, Yates A, Huehns ER. Idiopathic Heinz body anemia: Hb-Bristol (ß67 (E11) Val to Asp). Br J Haematol. 1970;18:435–446.CrossRefPubMedGoogle Scholar
  5. 5.
    Molchanova TP, Postnikov Yu V, Pobedimskaya DD, et al. Hb Alesha or α2 ß(2)67(Ell)Val → Met: a new unstable hemoglobin variant identified through sequencing of amplified DNA. Hemoglobin. 1993;17:217–225.CrossRefPubMedGoogle Scholar
  6. 6.
    Rees DC, Rochette J, Schofield C, et al. A novel silent posttranslational mechanism converts methionine to aspartate in hemoglobin Bristol (ß67[Ell] Val→Asp). Blood. 1996;88:341–348.PubMedGoogle Scholar
  7. 7.
    Hutt PJ, Fairbanks VF, Thibodeau SN, et al. Hb T-Cambodia, a ß chain variant with the mutations of Hb E and Hb D-Punjab, confirmed by DNA analysis. Hemoglobin. 1997;21:205–218.CrossRefPubMedGoogle Scholar
  8. 8.
    Miyazaki A, Nakanishi T, Shimizu A, Hisamitsu H. First case of a single heterozygote of an abnormal hemoglobin, Hb Stanmore. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;792:23–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Miyazaki A, Nakanishi T, Kishikawa M, et al. Post-translational modification from methionine to aspartic acid-residue on a variant hemoglobin, Hb Bristol, a proof by ESI-MS-MS. J Mass Spectrom. 1996;31:1311–1313.CrossRefPubMedGoogle Scholar
  10. 10.
    Ohba Y, Hattori Y, Harano T, Harano K, Fukumaki Y, Ideguchi H. ß-Thalassemia mutations in Japanese and Koreans. Hemoglobin. 1997;21:191–200.CrossRefPubMedGoogle Scholar
  11. 11.
    Cathie I. Apparent idiopathic Heinz body anemia. Great Ormond St J. 1952;3:43–47.Google Scholar
  12. 12.
    Sakuragawa M, Ohba Y, Miyaji T, Yamamoto K, Miwa S. A Japanese boy with hemolytic anemia due to an unstable hemoglobin (Hb Bristol). Nippon Ketsueki Gakkai Zasshi. 1984;47:896–902.PubMedGoogle Scholar
  13. 13.
    Ohba Y, Matsuoka M, Miyaji T, Shibuya T, Sakuragawa M. Hemoglobin Bristol or ß67(Ell) Val →Asp in Japan. Hemoglobin. 1985; 9:79–85.CrossRefPubMedGoogle Scholar
  14. 14.
    Aseeva EA, Lutsenko IN, Pivnik AV, Spivak VA, Beliaeva LS, Zhestkova NM. Congenital hemolytic anemia caused by the carriage of hemoglobin Bristol ß67 Bal→Asp. Ter Arkh. 1993;64:78–81.Google Scholar
  15. 15.
    Thein SL. Is it dominantly inherited ß thalassaemia or just a ß-chain variant that is highly unstable? Br J Haematol. 1999;107:12–21.CrossRefPubMedGoogle Scholar
  16. 16.
    Thein SL, Hesketh C, Taylor P, et al. Molecular basis for dominantly inherited inclusion body ß-thalassemia. Proc Natl Acad Sci USA. 1990;87:3924–3928.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Podda A, Galanello R, Maccioni L, et al. Hemoglobin Cagliari (ß60 [E4] Val →Glu): a novel unstable thalassemic hemoglobinopathy. Blood. 1991;15:371–375.Google Scholar
  18. 18.
    Baird M, Schreiner H, Driscoll C, Bank A. Localization of the site of recombination in formation of Lepore Boston globin gene. J Clin Invest. 1981;68:560–564.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Orkin SH, Antonakaris SE, Loukopoulaos D. Abnormal processing of ß Knossos RNA. Blood. 1984;64:311–313.PubMedGoogle Scholar
  20. 20.
    Orkin SH, Kazarian HH Jr, Antonarakis SE, Ostrer H, Goff SC, Sexton JP. Abnormal RNA processing due to the exon mutation of ß E-globin gene. Nature. 1982;300:768–769.CrossRefPubMedGoogle Scholar
  21. 21.
    Weiss IM, Liebhaber SA. Erythroid cell-specific mRNA stability elements in the α2-globin 3’ nontranslated region. Mol Cell Biol. 1995;15:2457–2465.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wajcman H, Vasseur C, Blouquit Y, et al. Hemoglobin Redondo [ß92 (F8) His →Asn]: an unstable hemoglobin variant associated with heme loss which occurs in two forms. Am J Hematol. 1991;38:194–200.CrossRefPubMedGoogle Scholar
  23. 23.
    Brenann SO, Shaw J, Allen J, George PM. Beta 141 Leu is not deleted in the unstable haemoglobin Atlanta-Coventry but is replaced by a novel amino acid of mass 129 daltons. Br J Haematol. 1992;81:99–103.CrossRefGoogle Scholar
  24. 24.
    Perutz MF. Frequency of abnormal human hemoglobins caused by C→T transitions in CpG dinucleotides. J Mol Biol. 1990;213:203–206.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Gen Kano
    • 1
  • Akira Morimoto
    • 1
  • Shigeyoshi Hibi
    • 1
  • Chika Tokuda
    • 1
  • Shinjiro Todo
    • 1
  • Tohru Sugimoto
    • 1
  • Teruo Harano
    • 2
  • Ayako Miyazaki
    • 3
  • Akira Shimizu
    • 3
  • Shinsaku Imashuku
    • 4
  1. 1.Department of PediatricsKyoto Prefectural University of MedicineKyoto
  2. 2.2nd Department of BiochemistryKawasaki Medical CollegeKurashiki
  3. 3.Department of Clinical PathologyOsaka Medical CollegeTakatsuki
  4. 4.Kyoto City Institute of Health and Environmental SciencesKyotoJapan

Personalised recommendations