A Rare Thalassemic Syndrome Caused by Interaction of Hb Adana [α59(E8)Gly→Asp] with an α+-Thalassemia Deletion: Clinical Aspects in Two Cases

Hb Adana is a highly unstable and rare α-globin hemoglobin (Hb) variant, to date described in only three families, in interaction with other α-thalassemia (α-thal) deletions. We describe the clinical and hematological findings in two cases from independent families of Albanian origin, who have an interaction of the codon 59 (Gly→Asp) α2-globin gene variant in trans to a 3.7 kb α+-thal deletion (αcodon 59α/−α). We report their presenting symptoms and laboratory findings as well as complications and differences in their clinical management. Both cases can be characterized as thalassemia intermedia and illustrate the problems associated with selecting the most appropriate options for patient management, especially in cases with rare underlying genotypes.

[1]  C. Borgna-Pignatti Modern treatment of thalassaemia intermedia , 2007, British journal of haematology.

[2]  T. Peto,et al.  Age-related changes in adaptation to severe anemia in childhood in developing countries , 2007, Proceedings of the National Academy of Sciences.

[3]  M. Cappellini,et al.  Thalassemia intermedia: revisited. , 2006, Blood cells, molecules & diseases.

[4]  S. Menon,et al.  Hb Sallanches [α104(G11)Cys→Tyr, TGC→TAC (α2)]: An Unstable Hemoglobin Variant Found in an Indian Child , 2006 .

[5]  M. Gladwin,et al.  The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. , 2005, JAMA.

[6]  I. Papassotiriou,et al.  A Rare 33 bp In‐Frame Deletion (α63–74 or α64–74 or α65–75) in the α1‐Globin Gene Causing α+‐Thalassemia: A Second Observation , 2004 .

[7]  H. Troxler,et al.  A New Highly Unstable α Chain Variant Causing α+‐Thalassemia: Hb Zurich Albisrieden [α59(E8)Gly→Arg (α2)] , 2004, Hemoglobin.

[8]  H. Wajcman,et al.  A new Unstable α2‐Globin Gene Variant: Hb Chartres [α33(B14)Phe→Ser] , 2003 .

[9]  D. J. Weatherall,et al.  Phenotype—genotype relationships in monogenic disease: lessons from the thalassaemias , 2001, Nature Reviews Genetics.

[10]  I. Papassotiriou,et al.  Phenotypic and molecular diversity of haemoglobin H disease: a Greek experience , 2000, British journal of haematology.

[11]  I. Papassotiriou,et al.  Distinct Phenotypic Expression Associated with a New Hyperunstable Alpha Globin Variant (Hb Heraklion, α1cd37(C2)Pro>0): Comparison to Other α-Thalassemic Hemoglobinopathies , 2000 .

[12]  I. Papassotiriou,et al.  Interaction of an α+-Thalassemia Deletion with Either a Highly Unstable α-Globin Variant (α2, Codon 59, GGC→GAC) or a Nondeletional α-Thalassemia Mutation (AATAA→AATAAG): Comparison of Phenotypes Illustrating “Dominant” α-Thalassemia , 1999 .

[13]  I. Papassotiriou,et al.  Rapid and accurate quantitation of Hb Bart's and Hb H using weak cation exchange high performance liquid chromatography: correlation with the alpha-thalassemia genotype. , 1999, Hemoglobin.

[14]  M. Tzetis,et al.  Prenatal diagnosis of the thalassaemia syndromes by rapid DNA analytical methods. , 1997, Molecular human reproduction.

[15]  V. Chan,et al.  Molecular defects in Hb H hydrops fetalis , 1997, British journal of haematology.

[16]  H. Wajcman,et al.  Chapter 2 Hemolytic anemias due to hemoglobinopathies , 1996 .

[17]  E. Kanavakis,et al.  The interaction of α° thalassaemia with Hb Icaria: three unusual cases of haemoglobinopathy H , 1996 .

[18]  T. Huisman,et al.  Hb adana or α259(E8)Gly→Aspβ2, A severely unstable α1‐globin variant, observed in combination with the ‐(α)20.5 KB α‐thal‐1 deletion in two Turkish patients , 1993 .

[19]  M. Tzetis,et al.  Characterization of nondeletion α‐thalassemia mutations in the Greek population , 1993 .

[20]  D. Labie,et al.  Unstable alpha‐chain hemoglobin variants with factitious beta‐thalassemia biosynthetic ratio: Hb questembert (α131[H14] Ser→Pro) and Hb Caen (α132[H15] Val→Gly) , 1993 .

[21]  S. Thein DOMINANT β THALASSAEMIA: MOLECULAR BASIS AND PATHOPHYSIOLOGY , 1992 .

[22]  M. Coleman,et al.  Structural hemoglobin variants that produce the phenotype of thalassemia. , 1990, Seminars in hematology.

[23]  J. Peristeri,et al.  Red Cell Alloantibodies in Patients with Thalassemia , 1990, Vox sanguinis.

[24]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[25]  I. Papassotiriou,et al.  Rare thalassemic syndrome caused by interaction of Hb Questembert (α1 codon 131, TCT>CCT, Ser>Pro) with an α-thalassemia-2 deletion: implications for diagnosis and management , 2004 .

[26]  T. Huisman,et al.  The Thalassemia Repository (Ninth Edition; Part II) , 1998 .