alpha thalassemia


Summary: A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted.

Top Publications

  1. Papachatzopoulou A, Kourakli A, Makropoulou P, Kakagianne T, Sgourou A, Papadakis M, et al. Genotypic heterogeneity and correlation to intergenic haplotype within high HbF beta-thalassemia intermedia. Eur J Haematol. 2006;76:322-30 pubmed
    ..The genetic determinant(s) of high HbF in the absence of HPFH is linked to intergenic haplotype T and does not disrupt intergenic transcription. ..
  2. Henderson S, Chapple M, Rugless M, Fisher C, Kinsey S, Old J. Haemoglobin H hydrops fetalis syndrome associated with homozygosity for the alpha2-globin gene polyadenylation signal mutation AATAAA-->AATA- -. Br J Haematol. 2006;135:743-5 pubmed
  3. Fowkes F, Michon P, Pilling L, Ripley R, Tavul L, Imrie H, et al. Host erythrocyte polymorphisms and exposure to Plasmodium falciparum in Papua New Guinea. Malar J. 2008;7:1 pubmed publisher
    ..falciparum infection. This contrasts with data for sickle cell trait and highlights that the above-mentioned polymorphisms may confer protection against malaria via distinct mechanisms. ..
  4. Wambua S, Mwangi T, Kortok M, Uyoga S, Macharia A, Mwacharo J, et al. The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med. 2006;3:e158 pubmed
  5. Higgs D, Weatherall D. The alpha thalassaemias. Cell Mol Life Sci. 2009;66:1154-62 pubmed publisher
  6. Shih H, Shih M, Chang Y, Peng C, Chang T, Chang J. Hb Hekinan in a Taiwanese subject: a G-->T substitution at codon 27 of the alpha1-globin gene abolishes an HaeIII site. Hemoglobin. 2007;31:495-8 pubmed
    ..Hb Hekinan [alpha27(B8)Glu-->Asp, GAG-->GAC (alpha2)] has not been found in Taiwan. This variant can be detected by high performance liquid chromatography (HPLC) but not by capillary or cellulose electrophoresis. ..
  7. Chui D. Alpha-thalassemia: Hb H disease and Hb Barts hydrops fetalis. Ann N Y Acad Sci. 2005;1054:25-32 pubmed
    ..These findings underscore the public health importance of these hereditary disorders, and they call for better education, diagnosis, treatment, prevention, and research for these diseases...
  8. Eng B, Patterson M, Walker L, Hoppe C, Azimi M, Lee H, et al. Three new alpha-thalassemia point mutations ascertained through newborn screening. Hemoglobin. 2006;30:149-53 pubmed
    ..The third mutation was a frameshift in exon 3 of the alpha2-globin gene, codons 113/114 (-C). This mutation was detected in a newborn who carried the 3.7 kb alpha(+)-thal deletion (alpha(T)alpha/-alpha(3.7)). ..
  9. Pan L, Eng H, Kuo C, Chen W, Huang H. Usefulness of brilliant cresyl blue staining as an auxiliary method of screening for alpha-thalassemia. J Lab Clin Med. 2005;145:94-7 pubmed
    ..We conclude that BCB staining is helpful and reliable as an auxiliary method of detecting HbH inclusions in the diagnosis of alpha-thalassemia traits, especially in places where medical resources are limited. ..

More Information


  1. Steensma D, Higgs D, Fisher C, Gibbons R. Acquired somatic ATRX mutations in myelodysplastic syndrome associated with alpha thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX mutations. Blood. 2004;103:2019-26 pubmed
  2. Neishabury M, Azarkeivan A, Najmabadi H. Frequency of positive XmnIGgamma polymorphism and coinheritance of common alpha thalassemia mutations do not show statistically significant difference between thalassemia major and intermedia cases with homozygous IVSII-1 mutation. Blood Cells Mol Dis. 2010;44:95-9 pubmed publisher
    ..To re-evaluate our current diagnostic criteria, XmnI(G)gamma polymorphism and coexistence of alpha thalassemia mutations, frequently recalled as important factors modifying the clinical phenotype of homozygous beta zero ..
  3. Harteveld C, Voskamp A, Phylipsen M, Akkermans N, den Dunnen J, White S, et al. Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterised by high resolution multiplex ligation-dependent probe amplification. J Med Genet. 2005;42:922-31 pubmed
    ..The approach as described here is a rapid and sensitive method for high resolution analysis of the globin gene clusters and for any region of the genome. ..
  4. Gibbons R, Pellagatti A, Garrick D, Wood W, Malik N, Ayyub H, et al. Identification of acquired somatic mutations in the gene encoding chromatin-remodeling factor ATRX in the alpha-thalassemia myelodysplasia syndrome (ATMDS). Nat Genet. 2003;34:446-9 pubmed
    ..These findings cast new light on this pleiotropic cofactor, which appears to be an essential component rather than a mere facilitator of globin gene expression. ..
  5. Yi J, Moertel C, Baker K. Homozygous alpha-thalassemia treated with intrauterine transfusions and unrelated donor hematopoietic cell transplantation. J Pediatr. 2009;154:766-8 pubmed publisher
    ..We present a patient with Hemoglobin Bart's disease who was cured after failing to engraft with 1 unrelated HCT, but engrafting after a second unrelated donor HCT. ..
  6. Enevold A, Lusingu J, Mmbando B, Alifrangis M, Lemnge M, Bygbjerg I, et al. Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania. Am J Trop Med Hyg. 2008;78:714-20 pubmed
  7. May J, Evans J, Timmann C, Ehmen C, Busch W, Thye T, et al. Hemoglobin variants and disease manifestations in severe falciparum malaria. JAMA. 2007;297:2220-6 pubmed
  8. Wambua S, Mwacharo J, Uyoga S, Macharia A, Williams T. Co-inheritance of alpha+-thalassaemia and sickle trait results in specific effects on haematological parameters. Br J Haematol. 2006;133:206-9 pubmed
    ..63 g/dl) than in HbAS children (0.25 g/dl). HbAS also ameliorated both the reduced mean cell volume and mean cell haemoglobin normally associated with the -alpha/-alpha genotype. Potential mechanisms and implications are discussed. ..
  9. Chan V, Ng E, Yam I, Yeung W, Ho P, Chan T. Experience in preimplantation genetic diagnosis for exclusion of homozygous alpha degrees thalassemia. Prenat Diagn. 2006;26:1029-36 pubmed
    ..Their genotypes were confirmed by cord blood analysis. PGD for alpha degrees thalassemia is possible by single cell PCR. The transfer and successful implantation of unaffected embryos ensure birth of disease-free babies. ..
  10. Al Allawi N, Badi A, Imanian H, Nikzat N, Jubrael J, Najmabadi H. Molecular characterization of alpha-thalassemia in the Dohuk region of Iraq. Hemoglobin. 2009;33:37-44 pubmed publisher
    ..All nine Hb H cases carried the -alpha(3.7)/- -(MED-I) genotype. Such findings are rather different from those in other eastern Mediterranean populations, particularly with relevance to an Hb H molecular basis. ..
  11. Neishabury M, Azarkeivan A, Oberkanins C, Esteghamat F, Amirizadeh N, Najmabadi H. Molecular mechanisms underlying thalassemia intermedia in Iran. Genet Test. 2008;12:549-56 pubmed publisher
    ..Some of the unresolved cases will offer an opportunity to discover additional molecular mechanisms leading to thalassemia intermedia. ..
  12. Lücke T, Pfister S, Dürken M. Neurodevelopmental outcome and haematological course of a long-time survivor with homozygous alpha-thalassaemia: case report and review of the literature. Acta Paediatr. 2005;94:1330-3 pubmed
    ..Early intervention during pregnancy and careful haematological as well as neuropsychological follow-up was able to provide long-term survival and good life quality in our patient. ..
  13. Liao C, Mo Q, Li J, Li L, Huang Y, Hua L, et al. Carrier screening for alpha- and beta-thalassemia in pregnancy: the results of an 11-year prospective program in Guangzhou Maternal and Neonatal hospital. Prenat Diagn. 2005;25:163-71 pubmed
    ..Our hospital-based program proved to be highly effective in reducing severe thals in pregnant populations. ..
  14. Williams T, Wambua S, Uyoga S, Macharia A, Mwacharo J, Newton C, et al. Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood. 2005;106:368-71 pubmed
    ..Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria. ..
  15. Denic S, Nicholls M. Genetic benefits of consanguinity through selection of genotypes protective against malaria. Hum Biol. 2007;79:145-58 pubmed
  16. Gibbons R. Alpha thalassaemia-mental retardation, X linked. Orphanet J Rare Dis. 2006;1:15 pubmed
    ..Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s. ..
  17. De Gobbi M, Viprakasit V, Hughes J, Fisher C, Buckle V, Ayyub H, et al. A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science. 2006;312:1215-7 pubmed
    We describe a pathogenetic mechanism underlying a variant form of the inherited blood disorder alpha thalassemia. Association studies of affected individuals from Melanesia localized the disease trait to the telomeric region of human ..
  18. Xu X, Zhou Y, Luo G, Liao C, Zhou M, Chen P, et al. The prevalence and spectrum of alpha and beta thalassaemia in Guangdong Province: implications for the future health burden and population screening. J Clin Pathol. 2004;57:517-22 pubmed
    ..The knowledge gained in this study will enable the projected number of pregnancies at risk to be estimated and a screening strategy for control of thalassaemia to be designed in this area. ..
  19. Enevold A, Alifrangis M, Sanchez J, Carneiro I, Roper C, Børsting C, et al. Associations between alpha+-thalassemia and Plasmodium falciparum malarial infection in northeastern Tanzania. J Infect Dis. 2007;196:451-9 pubmed
    ..falciparum transmission intensity. There was no evidence of population substructuring, and the results are suggestive of selection of the alpha (3.7) allele by malaria. ..
  20. Wajcman H, Traeger Synodinos J, Papassotiriou I, Giordano P, Harteveld C, Baudin Creuza V, et al. Unstable and thalassemic alpha chain hemoglobin variants: a cause of Hb H disease and thalassemia intermedia. Hemoglobin. 2008;32:327-49 pubmed publisher
    ..Genotype/phenotype correlation and potential genetic risk in combination with common or less common alpha-thal defects are discussed. ..
  21. Mockenhaupt F, Ehrhardt S, Gellert S, Otchwemah R, Dietz E, Anemana S, et al. Alpha(+)-thalassemia protects African children from severe malaria. Blood. 2004;104:2003-6 pubmed
    ..52; 95% CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of alpha(+)-thalassemia in Africa due to protection from severe malaria. ..
  22. Deng J, Peng W, Li J, Fang C, Liang X, Zeng Y, et al. Successful preimplantation genetic diagnosis for alpha- and beta-thalassemia in China. Prenat Diagn. 2006;26:1021-8 pubmed
    ..9% and 10.9%, respectively. These studies represent the successful applications of PGD protocols that can detect more than 95% of alpha- and beta -thalassemia mutations in the Chinese population. ..
  23. Durmaz A, Akin H, Ekmekci A, Onay H, Durmaz B, Cogulu O, et al. A severe alpha thalassemia case compound heterozygous for Hb Adana in alpha1 gene and 20.5 kb double gene deletion. J Pediatr Hematol Oncol. 2009;31:592-4 pubmed publisher
  24. Slomp J, Bosschaart A, Dousma M, van Zwieten R, Giordano P, van den Bergh F. [Acute anaemia in a Vietnamese patient with alpha-thalassaemia and a parvovirus infection]. Ned Tijdschr Geneeskd. 2006;150:1577-82 pubmed
    ..This case demonstrates that essentially asymptomatic carriership of thalassaemia can have serious consequences when coupled with a concurrent infection. ..
  25. Barresi V, Ragusa A, Fichera M, Musso N, Castiglia L, Rappazzo G, et al. Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome. BMC Med Genomics. 2010;3:28 pubmed publisher
    ..Moreover a novel alternative splicing transcript of such gene, predominantly expressed in brain tissues, was identified. ..
  26. Mackinnon M, Mwangi T, Snow R, Marsh K, Williams T. Heritability of malaria in Africa. PLoS Med. 2005;2:e340 pubmed
  27. Nyakeriga A, Troye Blomberg M, Mwacharo J, Wambua S, Williams T. Nutritional iron status in children with alpha+ thalassemia and the sickle cell trait in a malaria endemic area on the coast of Kenya. Haematologica. 2005;90:552-4 pubmed
    ..We found no support for this hypothesis in a cohort of children living on the coast of Kenya. ..
  28. Williams T, Mwangi T, Wambua S, Peto T, Weatherall D, Gupta S, et al. Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait. Nat Genet. 2005;37:1253-7 pubmed
    ..Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa. ..
  29. Imrie H, Fowkes F, Michon P, Tavul L, Hume J, Piper K, et al. Haptoglobin levels are associated with haptoglobin genotype and alpha+ -Thalassemia in a malaria-endemic area. Am J Trop Med Hyg. 2006;74:965-71 pubmed
    ..We suggest that this is the result of either reduced mean cell Hb associated with alpha(+) -thalassemia homozygosity or an elevated IL-6-dependent acute phase response. ..
  30. Wada T, Sugie H, Fukushima Y, Saitoh S. Non-skewed X-inactivation may cause mental retardation in a female carrier of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X): X-inactivation study of nine female carriers of ATR-X. Am J Med Genet A. 2005;138:18-20 pubmed
    ..These findings suggest that mutations in ATRX may cause mental retardation in females, if the X chromosome carrying mutated ATRX is not properly inactivated...
  31. Mockenhaupt F, Ehrhardt S, Otchwemah R, Eggelte T, Anemana S, Stark K, et al. Limited influence of haemoglobin variants on Plasmodium falciparum msp1 and msp2 alleles in symptomatic malaria. Trans R Soc Trop Med Hyg. 2004;98:302-10 pubmed
    ..In symptomatic children, the effect of Hb variants on parasite multiplicity and diversity appears to be limited. This may reflect an actual lack of influence or indicate abrogation in symptomatic malaria. ..
  32. Liao C, Wei J, Li Q, Li J, Li L, Li D. Nonimmune hydrops fetalis diagnosed during the second half of pregnancy in Southern China. Fetal Diagn Ther. 2007;22:302-5 pubmed
    ..To analyze the etiologies of nonimmune hydrops fetalis (NIHF) for a southern section of China...
  33. Beutler E, West C. Hematologic differences between African-Americans and whites: the roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood. 2005;106:740-5 pubmed
    ..1% and 2.77% and to 4.29% and 3.6%, respectively. Physicians need to take into account that the same reference standards for hemoglobin, hematocrit, MCV, and TS and the white blood cell count do not apply to all ethnic groups. ..
  34. Ngiwsara L, Srisomsap C, Winichagoon P, Fucharoen S, Svasti J. Two cases of compound heterozygosity for Hb Hekinan [alpha27(B8)Glu-->Asp (alpha1)] and alpha-thalassemia in Thailand. Hemoglobin. 2004;28:145-50 pubmed
    ..However IEF gave good separation of Hb Hekinan and Hb A, leading to estimates of Hb Hekinan (alpha Hekinan 2/beta A 2 and alpha Hekinan 2/beta E 2) level as 40-43% of total Hb. ..
  35. Cockburn I, Mackinnon M, O Donnell A, Allen S, Moulds J, Baisor M, et al. A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria. Proc Natl Acad Sci U S A. 2004;101:272-7 pubmed
    ..We have therefore identified CR1 as a new malaria resistance gene and provided compelling evidence that rosetting is an important parasite virulence phenotype that should be a target for drug and vaccine development. ..
  36. Vichinsky E. Changing patterns of thalassemia worldwide. Ann N Y Acad Sci. 2005;1054:18-24 pubmed
    ..Comprehensive services that address language and social barriers as well as access to Hb F-enhancing agents and transfusions are needed. ..
  37. Lee S, Chow C, Li C, Chiu M. Outcome of intensive care of homozygous alpha-thalassaemia without prior intra-uterine therapy. J Paediatr Child Health. 2007;43:546-50 pubmed
    ..Without prior intra-uterine therapy, homozygous alpha-thalassaemia has grave outlook in terms of mortality and morbidity despite aggressive respiratory therapy. ..
  38. Origa R, Sollaino M, Giagu N, Barella S, Campus S, Mandas C, et al. Clinical and molecular analysis of haemoglobin H disease in Sardinia: haematological, obstetric and cardiac aspects in patients with different genotypes. Br J Haematol. 2007;136:326-32 pubmed
    ..0001). In the Sardinian population, Hb H disease needs regular monitoring for early detection and treatment of possible complications, such as worsening of anaemia that may require red cell transfusion, cholelithiasis and iron overload. ..
  39. Denic S, Frampton C, Nagelkerke N, Nicholls M. Consanguinity affects selection of alpha-thalassemia genotypes and the size of populations under selection pressure from malaria. Ann Hum Biol. 2007;34:620-31 pubmed
    ..Under selection pressure from malaria, consanguinity may increase the speed of selection of-alpha/-alpha homozygotes and provide an advantage regarding population growth over non-consanguineous populations. ..
  40. Laosombat V, Viprakasit V, Chotsampancharoen T, Wongchanchailert M, Khodchawan S, Chinchang W, et al. Clinical features and molecular analysis in Thai patients with HbH disease. Ann Hematol. 2009;88:1185-92 pubmed publisher
  41. Williams T, Weatherall D, Newbold C. The membrane characteristics of Plasmodium falciparum-infected and -uninfected heterozygous alpha(0)thalassaemic erythrocytes. Br J Haematol. 2002;118:663-70 pubmed
    ..We hypothesize that altered red-cell membrane band 3 protein may be a target for enhanced antibody binding to alpha-thalassaemic IRBCs and could be involved in the mechanism of malaria protection. ..
  42. Viprakasit V, Green S, Height S, Ayyub H, Higgs D. Hb H hydrops fetalis syndrome associated with the interaction of two common determinants of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)). Br J Haematol. 2002;117:759-62 pubmed
    ..Here we show for the first time that the interaction between two relatively common forms of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)) may be associated with a clinically severe form of alpha thalassaemia, Hb H hydrops fetalis...
  43. Gibbons R, Suthers G, Wilkie A, Buckle V, Higgs D. X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis. Am J Hum Genet. 1992;51:1136-49 pubmed
    ..Furthermore, they represent an important step in developing strategies to understand how the mutant ATR-X allele causes mental handicap, dysmorphism, and down-regulation of the alpha-globin genes. ..
  44. Kanavakis E, Papassotiriou I, Karagiorga M, Vrettou C, Metaxotou Mavrommati A, Stamoulakatou A, et al. Phenotypic and molecular diversity of haemoglobin H disease: a Greek experience. Br J Haematol. 2000;111:915-23 pubmed
    ..Together with the long-term follow-up in many patients, this report provides comprehensive information for management of Hb H disease and appropriate family counselling. ..
  45. Lacan P, Aubry M, Couprie N, Francina A. Hb Gerland [alpha55(E4)Val-->Ala (alpha2)]: a new neutral alpha chain variant involving the alpha2 gene. Hemoglobin. 2001;25:417-20 pubmed
  46. Chan V, Wong M, Ooi C, Chen F, Chim C, Liang R, et al. Can defects in transferrin receptor 2 and hereditary hemochromatosis genes account for iron overload in HbH disease?. Blood Cells Mol Dis. 2003;30:107-11 pubmed
  47. Lorey F, Charoenkwan P, Witkowska H, Lafferty J, Patterson M, Eng B, et al. Hb H hydrops foetalis syndrome: a case report and review of literature. Br J Haematol. 2001;115:72-8 pubmed
  48. Dame C, Albers N, Hasan C, Bode U, Eigel A, Hansmann M, et al. Homozygous alpha-thalassaemia and hypospadias--common aetiology or incidental association? Long-term survival of Hb Bart's hydrops syndrome leads to new aspects for counselling of alpha-thalassaemic traits. Eur J Pediatr. 1999;158:217-20 pubmed
    ..On the basis of our findings, we speculate that an unknown gene on chromosome 16 responsible for genital formation is altered in homozygous alpha-thalassaemia. ..
  49. Wada T, Nakamura M, Matsushita Y, Yamada M, Yamashita S, Iwamoto H, et al. [Three Japanese children with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X)]. No To Hattatsu. 1998;30:283-9 pubmed
    ..ATR-X should be considered as a differential diagnosis in all male patients with severe mental retardation. ..
  50. Fucharoen S, Changtrakun Y, Ratanasiri T, Fucharoen G, Sanchaisuriya K. Complex interaction of Hb Hekinan [alpha27(B8) Glu-Asp] and Hb E [beta26(B8) Glu-Lys] with a deletional alpha-thalassemia 1 in a Thai family. Eur J Haematol. 2003;70:304-9 pubmed
    ..The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies is presented and a simple DNA assay based on the polymerase chain reaction methodology for rapid diagnosis of Hb Hekinan is described. ..
  51. Abidi F, Schwartz C, Carpenter N, Villard L, Fontes M, Curtis M. Carpenter-Waziri syndrome results from a mutation in XNP. Am J Med Genet. 1999;85:249-51 pubmed
  52. Villard L, Gecz J, Mattei J, Fontes M, Saugier Veber P, Munnich A, et al. XNP mutation in a large family with Juberg-Marsidi syndrome. Nat Genet. 1996;12:359-60 pubmed
  53. Gibbons R, Picketts D, Villard L, Higgs D. Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome). Cell. 1995;80:837-45 pubmed
    ..In addition to its role in the ATR-X syndrome, XH2 may be a good candidate for other forms of X-linked mental retardation mapping to Xq13. ..