Alpha(0)-thalassemia is the most severe form of alpha-thalassemia commonly encountered in Asians. To provide relevant information for effective prevention and control of this disorder, we have examined the molecular basis and hematological features of alpha(0)-thalassemia-related disorders in northeast Thailand. A multiplex polymerase chain reaction for simultaneous detection of the southeast Asian (SEA) and the THAI alpha(0)-thalassemia determinants was developed and used for screening of 1,541 Thai individuals who were positive at the preliminary screening in an ongoing thalassemia control program. Alpha(0)-thalassemia deletions were detected in 397 (25.8%) cases, 396 with the SEA deletion and 1 with the THAI deletion. While the latter was found in association with the Hb Constant Spring in a patient with severe Hb H disease, the former was encountered in as many as 12 thalassemia genotypes whose hematological features were comparatively presented. The results obtained should prove useful in carrier screening and prenatal diagnosis programs of this common genetic disorder in the region.

Alpha(0)-thalassemia and related disorders in northeast Thailand: a molecular and hematological characterization.

Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China

Iron deficiency anemia in a dog

Study on the phenotypic expression of hemoglobin (Hb) A(2) and Hb E in Hb E disorders has been difficult due to the co-separation of Hb A(2) and Hb E in most Hb analysis assays. Because these two Hbs are separated on capillary electrophoresis, we studied phenotypic expression of Hbs A(2), E and F in various Hb E disorders using this system. This was done on 362 subjects with several Hb E disorders including heterozygous Hb E, homozygous Hb E, β-thalassemia/Hb E, δβ-thalassemia/Hb E, and Hb Lepore/Hb E and those of these disorders with several forms of α-thalassemia. Normal controls showed Hb A(2) of 2.7 ± 0.3%. Heterozygous Hb E and homozygous Hb E had elevated Hb A(2) i.e. 3.8 ± 0.3% and 4.8 ± 0.5%, respectively. Further elevations were observed for β(0)-thalassemia/Hb E (6.1 ± 1.9%) and β(+)-thalassemia/Hb E (7.1 ± 1.2%). Interestingly, no elevation of Hb A(2) was found in the δβ-thalassemia/Hb E, and Hb Lepore/Hb E (2.3 ± 0.3%) but higher Hb F levels were noted which could be useful diagnostic markers. The levels of Hb E were variable. Co-inheritance of these Hb E disorders with α-thalassemia were associated with lower outputs of Hb E and Hb F but the levels of Hb A(2) were not altered. Different phenotypic expression of Hb A(2), Hb E and Hb F could help in differential diagnosis of these Hb E related disorders commonly encountered in the regions where access to molecular techniques is limited.

Phenotypic expression of hemoglobins A₂, E and F in various hemoglobin E related disorders.

Synthesis of alpha-globin and alpha-globin subunits of hemoglobin occurs at high levels during erythrocyte differentiation in a tightly controlled and coordinated fashion Expression of alpha-globin is a fascinatingly complex process which has been meticulously defined in several recent studies, from chromatin modifications to Pol II recruitment Following this, alpha-globin transcripts are processed and stabilized by a protein complex which binds the 3' untranslated region Transcription and stabilization contribute to high level expression of alpha-globin However, translation of alpha-globin at levels exceeding alpha-globin expression damages cellular membranes and results in beta-thalassemia It is, therefore, crucial that alpha-globin proteins are properly folded and stabilized, processes which are dependent on the presence of haem and AHSP The exceedingly well-characterized process of alpha-globin expression elegantly illustrates the complex interaction of factors which are required to balance necessary high expression against the negative impacts of overexpression

Controlling α-globin: a review of α-globin expression and its impact on β-thalassemia

We describe hematologic and DNA characterization of hemoglobin (Hb) E homozygote with various forms of α-thalassemia in Thai individuals. Altogether, 131 unrelated adult subjects with Hb EE at routine Hb analysis were studied. Forty-two cases were found to carry α-thalassemia with ten different genotypes. These included 21 cases with α+-thalassemia heterozygote (–α3.7/αα), one case with α+-thalassemia heterozygote (–α4.2/αα), six cases with Hb Constant Spring heterozygote (αCSα/αα), four cases with homozygous α+-thalassemia (–α3.7/–α3.7), one case with homozygous α+-thalassemia (–α4.2/–α4.2), two cases with compound α+-thalassemia/Hb Constant Spring (–α3.7/αCSα), one case with compound α+-thalassemia/Hb Pakse (–α3.7/αPSα), four cases with α0-thalassemia heterozygote (––SEA/αα), and, unexpectedly, two cases with compound α0-thalassemia/α+-thalassemia [(––SEA/–α3.7) and (––SEA/–α4.2)]. The hematological expression of these Hb E homozygotes with various forms of α-thalassemia was presented comparatively with those of the 89 cases of pure Hb E homozygotes. Overlapping levels of Hb E, Hb F, and other hematological parameters were observed which did not predict clinical severity, indicating a need for α-globin gene analysis for accurate diagnosis and improved genetic counseling.

Molecular and hematological profiles of hemoglobin EE disease with different forms of α-thalassemia

In order to obtain an appropriate control measure for thalassemia and iron deficiency anemia, it is necessary to estimate the health burden in the relevant area. This study aimed to determine the prevalence of thalassemia and iron deficiency in pregnant women attending antenatal care service at Khaowong Hospital, Kalasin province, in which the majority of pregnant women is the “PhuTai” ethnic group. Blood samples taken from 302 pregnant women were investigated for hematological parameters using an automated blood cell counter to diagnose anemia. For the diagnosis of iron deficiency, measurement of ferritin was done by chemiluminescent immunoassay. Hb analysis using cellulose acetate electrophoresis and/or capillary zone electrophoresis was performed to diagnose b -thalassemia and abnormal hemoglobin (Hb). Alpha-thalassemia genes including Hb Constant Spring (Hb CS) and Hb Pakse’ were identified by the polymerase chain reaction and related technologies. Of the 302 subjects, 36.4 % (95% CI = 31.0-42.1) had anemia, 42.0 % (95 % CI = 32.2-52.3) had iron deficiency and 17.0 % (95 % CI = 10.2-25.8) had iron deficiency anemia. Alpha-thalassemia 1 was found in 9.6% (95% CI = 6.5-13.5), comprising 9.3 % SEA deletion and 0.3 % THAI deletion. The prevalence of a -thalassemia 2 was 27.0 % (95 % CI = 18.6-36.8), comprising 14.0 % 3.7 kb deletion, 1.0 % 4.2 kb deletion and 12 % Hb CS. While 43.7 % (95 % CI = 38-0-49.5) of the subjects were Hb E carriers, only 0.3% (95 % CI = 0.0-1.8) were b -thalassemia carriers. The findings demonstrate the health burden in relation to thalassemia and iron deficiency anemia and indicate a need for appropriate measure to control the disease in this ethnic group.

Jaruwan Trithipsombat

Papers

Molecular and hematological profiles of hemoglobin EE disease with different forms of α-thalassemia

Thalassemia and iron deficiency among pregnant women attending antenatal care service at Khao Wong Hospital, Kalasin province