Background/Aims: Individuals with double heterozygosity for α- and β-thalassaemia and heterozygous β-thalassaemia show a similar haematological picture. Co-inheritance of α- and β-thalassaemia in both partners may result in pregnancies with either Hb Bart’s hydrops foetalis or β-thalassaemia major, or pregnancies with both disorders. Methods: The co-inheritance of α-thalassaemia in 322 β-thalassaemia carriers in Malaysia was studied. Results: The frequency of α-thalassaemia in the β-thalassaemia carriers was 12.7% (41/322), with a carrier frequency of 7.8% for the SEA deletion, 3.7% for the -α3.7 deletion, 0.9% for Hb Constant Spring and 0.3% for the -α4.2 deletion. Conclusion: Double heterozygosity for α- and β-thalassaemia was confirmed in 5 out of the 41 couples and the risk of the fatal condition Hb Bart’s hydrops foetalis was confirmed in two of these couples. Detection of the Southeast Asian (SEA) deletion in the Malaysian Malays in this study confirms that Hb Bart’s hydrops foetalis can occur in this ethnic group. Results of this study have provided new information on the frequency and different types of α-thalassaemia (--SEA, -α3.7 and -α4.2 deletions, Hb Constant Spring) in Malaysian β-thalassaemia carriers.

Keywords:
α-Thalassaemia, β-Thalassaemia, Southeast Asian deletion, Hb Bart’s hydrops foetalis, Amplification refractory mutation system, Gap-PCR, PCR-RFLP, Duplex PCR
1.
Pootrakul S, Wasi P, Na-Nakorn S: Haemoglobin Bart’s hydrops in Thailand. Ann Hum Genet 1967;30:293–311.
2.
Ottolenghi S, Lanyon WG, Paul J, Williamson R: Gene deletion as the cause of α-thalassaemia. Nature 1974;251:389–391.
3.
Kan YW, Schwartz E, Nathan DG: Globin chain synthesis in the alpha thalassemia syndromes. J Clin Invest1969;47:2512–2522.
4.
George E: Thalassaemia Carrier Diagnosis in Malaysia. Kuala Lumpur, SP-Muda, 1998.
5.
Wee YC, Tan KL, Chow TWP, Yap SF, Tan JAMA: Heterogeneity in α-thalassemia interactions in Malays, Chinese and Indians in Malaysia. J Obstet Gynaecol Res 2005;31:540–546.
6.
Clegg JB, Weatherall DJ, Milner PF: Hemoglobin Constant Spring – a chain termination mutant? Nature1971;234:337.
7.
Weatherall DJ, Clegg JB, Na-Nakorn S, Wasi P: The pattern of disordered haemoglobin synthesis in homozygous and heterozygous β-thalassaemia. Br J Haematol 1969;16:251–267.
8.
Tan JAMA, George E, Tan KL, Chow T, Tan PC, Hassan J, Chia P, Subramanium R, Chandran R, Yap SF: Molecular defects in the beta-globin gene identified in different ethnic groups/populations during prenatal diagnosis for beta-thalassaemia: a Malaysian experience. Clin Exp Med 2004;4:142–147.
9.
Wanapirak C, Muninthorn W, Sanguansermsri T, Dhananjayanonda P, Tongsong T: Prevalence of thalassaemia in pregnant women at Maharaj Nakorn Chiang Mai Hospital. J Med Assoc Thai 2004;87:1415–1418.
10.
Ko TM, Cavilas AP Jr, Hwa HL, Liu CW, Hsu PM, Chung YP: Prevalence and molecular characterization of beta-thalassaemia in Filipinos. Ann Hematol 1998;77:257–260.
11.
Lau YL, Chan LC, Chan YY, Ha SY, Yeung CY, Waye JS, Chui DH: Prevalence and genotypes of alpha- and beta-thalassaemia carriers in Hong Kong – implications for population screening. N Engl J Med 1997;336:1298–1301.
12.
Ghosh A, Woo JS, Wan CW, Machenry C, Wong V, Ma HK, Chan V, Chan TK: Evaluation of a prenatal screening procedure for beta-thalassaemia carriers in a Chinese population based on the mean corpuscular volume (MCV). Prenat Diagn 1985;5:59–65.
13.
Xu XM, Zhou YQ, Luo GX, Liao C, Zhao M, Chen PY, Lu JP, Jia SQ, Xiao GF, Shen X, Li J, Chen HP, Xia YY, Wen YX, Mo QH, Li WD, Li YY, Zhuo LW, Wang ZQ, Chen YJ, Qin CH, Zhong M: The prevalence and spectrum of α and β thalassaemia in Guangdong Province: implications for the future health burden and population screening. J Clin Pathol 2004;57:517–522.
14.
Fucharoen S, Winichagoon P, Thonglairuam V: Beta-thalassaemia associated with alpha-thalassaemia in Thailand. Hemoglobin 1988;12:581–592.
15.
Lam YH, Ghosh A, Tang MHY, Chan V: The risk of α-thalassaemia in offspring of β-thalassaemia carriers in Hong Kong. Prenat Diagn 1997;17:733–736.
16.
Chong YM, Tan JAMA, Zubaidah Z, Rahimah A, Kuldip K, George E: Screening of concurrent α-thalassaemia 1 in β-thalassaemia carriers. Med J Malaysia 2006;61:1–4.
17.
Chan V, Chan TK, Cheng MY, Kan YW, Todd D: Organization of the ζ-α genes in Chinese. Br J Haematol 1986;64:97–105.
18.
Ma SK, Chan YY, Ha SY, Chan CF, Lau YL, Chan LC: Screening for (–SEA) α-globin gene deletion in β-thalassaemia carriers and prevention of hydrops foetalis. Haematologica 2000;85:991–993.
19.
Han J, Zeng R, Hu B: The prevalence of beta-thalassaemia heterozygotes compound alpha-thalassaemia in Guangdong district. Zhonghua Xue Ye Xue Za Zhi 2001;22:514–516.
20.
Prevention of Thalassaemias and Other Haemoglobin Disorders, vol 2: Laboratory Methods. Nicosia, Thalassaemia International Federation, 2005.
21.
Chan YF, Tan KL, Wong YC, Wee YC, Yap SF, Tan JAMA: The use of the amplification refractory mutation system (ARMS) in the detection of rare β-thalassemia mutations in the Malays and Chinese in Malaysia. Southeast Asian J Trop Med Public Health 2001;32:872–879.
22.
Motum PI, Kearney A, Hamilton TJ, Trent R: Filipino β0 thalassemia: a high Hb A2 β0 thalassemia resulting from a large deletion of the 5′ β-globin gene region. J Med Genet 1993;30:240–244.
23.
Eng B, Chui DH, Saunderson J, Olivieri NF, Waye JS: Identification of two novel β0 thalassemia mutations in a Filipino family: frameshift codon 67 (-TG) and a β-globin gene deletion. Hum Mutat 1993;2:375–379.
24.
Craig JE, Barnetson RA, Prior J, Raven JL, Thein SL: Rapid detection of deletions causing δβ thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification. Blood 1994;83:1673–1682.
25.
Wee YC, Tan KL, Tan PC, Yap SF, Tan JAMA: Rapid and cost-effective antenatal diagnosis of haemoglobin Bart’s hydrops foetalis syndrome using a duplex-polymerase chain reaction. Med J Malaysia 2005;60:447–453.
26.
Proudfoot NJ, Maniatis T: The structure of a human α-globin pseudogene and its relationship to α-globin gene duplication. Cell 1980;21:537–544.
27.
Baysal E, Huisman THJ: Detection of common deletional α-thalassemia-2 determinants by PCR. Am J Hematol1994;46:208–213.
28.
Hsia YE, Ford CA, Shapiro LJ, Hunt JA, Ching NSP: Molecular screening for hemoglobin Constant Spring. Lancet 1989;i:988–991.
29.
Waye JS, Chui DH: The α-globin gene cluster: genetics and disorders. Clin Invest Med 2001;24:103–109.
30.
Siriratmanawong N, Fucharoen G, Sanchaisuriya K, Ratnasiri T, Fucharoen S: Simultaneous PCR detection of β-thalassaemia and α-thalassaemia 1 (SEA type) in prenatal diagnosis of complex thalassemia syndrome. Clin Biochem 2001;34:377–380.
31.
Li D, Liao C, Li J, Xie X, Huang Y, Zhong H: Detection of alpha-thalassemia in beta-thalassemia carriers and prevention of Hb Bart’s hydrops fetalis through prenatal screening. Haematologica 2006;91:649–651.
32.
George E, Selamah G: Hemoglobin Bart’s in cord blood of Malaysians. Southeast Asian. J Trop Med Public Health 1981;12:87–89.
33.
Winichagoon P, Fucharoen S, Wasi P: The molecular basis of alpha-thalassemia in Thailand. Southeast Asian J Trop Med Public Health 1992;23(suppl 2):7–13.
34.
Sriroongrueng W, Pornpatkul M, Panich V, Fucharoen S: Alpha-thalassemia incidence in southern Thailand by restriction endonuclease analysis of globin DNA from placental blood at Songklanagarind Hospital. Southeast Asian J Trop Med Public Health 1997;28(suppl 3):93–96.
35.
Ma SK, Chan YY, Ha SY, Chan CF, Au WY, Chan LC: The (--SEA) α-thalassaemia (SEA) deletion ameliorates the clinical phenotype of β0/β+ but not necessarily that of β0/β0 thalassemia. Haematologica 2002;87:443–444.
36.
Qatanani M, Taher A, Koussa S, Naaman R, Fisher C, Rugless M, Old J, Zahed L: Beta-thalassaemia intermedia in Lebanon. Eur J Haematol 2000;64:237–244.
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2008
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