Secondary erythrocytosis caused by hemoglobin Tak/(뫧)0-thalassemia syndrome.

Secondary erythrocytosis may arise from several causes, but an association with oxygen transport is rare. We describe for the first time a form of secondary erythrocytosis caused by compound heterozygosity for hemoglobin (Hb) Tak and (δß)(0)-thalassemia found in an adult Thai individual. The patient had marked erythrocytosis and microcytosis with increased Hb and hematocrit values. Hb analyses using the Hb Gold Analyzer showed Hb A2 (72.5%) and Hb F (30.0%) without Hb A while the capillary electrophoresis revealed 2.3% Hb A2 and a major peak of Hb F (91.2%). Further molecular investigation identified that he was in fact a compound heterozygote for Hb Tak and deletional (δß)(0)-thalassemia. Hematological parameters of the patient were compared with those observed for a Thai boy who demonstrated features of erythrocytosis and microcytosis caused by homozygous Hb Tak with α(+)-thalassemia and with those of pure carriers of Hb Tak and (δß)(0)-thalassemia in our series. This report confirms the importance of both Hb and molecular investigations for the assessment of genotype/phenotype correlation and the appropriate management of the patients.

Compound heterozygote state for GgammaAgamma(deltabeta) degrees -thalassemia and hereditary persistence of fetal hemoglobin.

We report a hitherto undescribed interaction of a deletional (deltabeta) degrees -thalassemia and a deletional hereditary persistence of fetal hemoglobin (HPFH) in an adult Thai individual. He was a 40-year-old Thai male who had the following hematologic data: Hb 13.9 g/dL, Hct 43.8%, MCV 78.0 fL, MCH 24.7 pg, MCHC 31.6 g/dL, and RDW 17.1%. Hemoglobin analysis revealed 97% Hb F with Ggamma-globin chain predominant. Globin gene analyses demonstrated that he carried the GgammaAgamma(deltabeta) degrees -thalassemia deletion in trans to the HPFH-6. Hematologic data of the patient were compared to those of the heterozygotes for these high-Hb F determinants found in his parents and an unrelated Thai patient with a compound HPFH-6/deletion-inversion Ggamma(Agammadeltabeta) degrees -thalassemia previously described.

Compound heterozygote states for Hb C/Hb Malay and Hb C/Hb E in pregnancy: a molecular and hematological analysis.

Hemoglobin (Hb) C (alpha2beta(2)6Glu-Lys) is a variant Hb found mainly in West Africa where individuals carrying both Hb C and Hb S (alpha2beta(2)6Glu-Val) usually have a disease similar to sickle cell disease. The Hb C molecule has reduced solubility leading to crystal formation and hemolytic anemia. We report a hitherto undescribed interaction of Hb C and Hb Malay (alpha2beta(2)19Asn-Ser) in a Thai individual. She was a 24-year-old pregnant woman with moderate anemia who had the following hematologic data; Hb 8.9 g/dl, Hct 30.0%, MCV 81.0 fl, MCH 24.1 pg, MCHC 29.7 g/dl, RDW 17.1% and instead of Hb crystal a marked number of target cell in peripheral blood was observed. Hb analysis revealed 22.5% Hb Malay, 64.6% Hb C and 4.5% Hb A2. Globin gene analyses demonstrated that she carried the betaC mutation (beta6: GAG-AAG) in trans to the betaMalay mutation (beta19: AAC-AGC). Hematologic data of the patient were compared to those of the compound heterozygote for Hb C and Hb E (alpha2beta(2)26Glu-Lys) found in 5 other unrelated Thai pregnant women and 11 pregnant women with Hb C heterozygote with or without co-inheritance of alpha-thalassemia who had much lower Hb C levels and the non-pregnant women with Hb C heterozygote and a compound Hb E/Hb Malay syndrome. Different genotype-phenotype correlations observed in these Thai patients with Hb C disorders are illustrated.

Molecular basis and hematologic characterization of deltabeta-thalassemia and hereditary persistence of fetal hemoglobin in Thailand.

BACKGROUND AND OBJECTIVES: Hereditary persistence of fetal hemoglobin (HPFH) and deltabeta-thalassemia are heterogeneous disorders characterized by increased levels of Hb F in adult life. The distinction between these two conditions is not always possible from routine hematologic analyses. This study investigated the hematologic and molecular characteristics of high HbF determinants in Thailand, and describes a rapid DNA-based assay to facilitate diagnosis in a routine laboratory. DESIGN AND METHODS: A multiplex allele-specific polymerase chain reaction (PCR) system for rapid detection of three common DNA deletions causing (deltabeta)0-thalassemia and HPFH in South-east Asians was developed and used to examine the molecular basis for the high Hb F phenotypes in 273 unrelated Thai individuals. Hematologic data were recorded and correlated to the molecular findings. RESULTS: The multiplex PCR system was validated and results were completely concordant with those of other established methods. DNA analysis identified GgAg(deltabeta)0-thalassemia in 148 cases (54.2%), deletional HPFH-6 in 83 (30.4 %) and the deletion-inversion Ggamma(Agammadeltabeta)0-thalassemia in 22 (8.1 %) cases, while another 20 (7.3 %) subjects remained uncharacterized. Genotype-phenotype relationships are discussed. INTERPRETATION AND CONCLUSIONS: These data emphasize the high frequencies of deltabeta-thalassemia and HPFH in Thailand and the need for differential diagnostic methods since the hematologic parameters associated with the conditions are very similar and overlap. The multiplex allele-specific PCR approach should prove useful in complementing routine Hb analysis for the differential diagnosis of these three common causes of high Hb F determinants and should facilitate a program of hemoglobinopathy screening in the region.

Molecular characterization of thalassemia intermedia associated with HPFH-6/beta-thalassemia and HPFH-6/Hb E in Thai patients.

We report the molecular and hematological characterizations of thalassemia caused by interactions of the hereditary persistence of fetal hemoglobin (HPFH)-6 with beta-thalassemia in 2 Thai patients and the HPFH-6 with Hb E in another Thai patient. Marked hypochromic microcytosis, characteristics of thalassemia intermedia, were obvious in the former 2 cases but the latter had much milder clinical phenotype with normal Hb and a slightly reduced mean corpuscular volume (MCV) value. Hb analysis revealed no Hb A but Hb A(2)F patterns in the compound HPFH-6/beta-thalassemia patients and the EF pattern in the HPFH-6/Hb E patient. The (G)gamma-globin chain predominated in all cases. Globin gene analyses demonstrated that all patients carried the 101-kb HPFH-6 deletion in trans to the beta-thalassemia genes with the IVS1#5 G-C mutation and the G insertion between codons 8/9 and the beta(E)-gene, respectively. Hematologic data of the patients were compared to those of the HPFH-6 heterozygotes found in their family members and different genotype-phenotype interactions of this HPFH determinant in these Thai patients are illustrated.

Molecular and hematological characterization of HPFH-6/Indian deletion-inversion Ggamma(Agammadeltabeta)0-thalassemia and Ggamma(Agammadeltabeta)0-thalassemia/HbE in Thai patients.

The hereditary persistence of fetal hemoglobin (HPFH)-6 is sporadically found in Thailand whereas the deletion-inversion type (G)gamma((A)gamma delta beta)(0)-thalassemia is described among Indians. We report a hitherto un-described case in which these two defects co-segregate. He was a 3-year-old Thai boy who had a feature of thalassemia intermedia phenotype with the following hematologic data; Hb 8.8 g/dL, Hct 29.2%, MCV 66.9 fL, MCH 20 pg, and MCHC 30.1 g/dL. Hemoglobin analysis revealed 100% Hb F with only (G)gamma-globin chain. Globin gene analyses demonstrated that he carried the HPFH-6 deletion in trans to the Indian deletion-inversion (G)gamma((A)gamma delta beta)(0)-thalassemia. Hematologic data of the patient was compared to those of the HPFH-6 heterozygote found in his father, to (G)gamma((A)gamma delta beta)(0)-thalassemia heterozygotes detected in his mother and sister, and to that of an unrelated Thai patient who was a compound heterozygote for the deletion-inversion (G)gamma((A)gamma delta beta)(0)-thalassemia and HbE.