Comparison of haemoglobin H inclusion bodies with embryonic ζ globin in screening for α thalassaemia

Aims - To compare the haemoglobin (Hb) H inclusion test with immunocytochemical detection of embryonic ζ chains in screening for a thalassaemia. Methods - Blood samples from 115 patients with relevant clinical history and hypochromic microcytic indexes were screened using the HbH inclusion test and the Variant Hemoglobin Testing System (BioRad, Hercules, CA, USA). Results - The HbH inclusion test was positive in 61 of 115 cases, three of whom had HbH disease confirmed by electrophoresis. The remaining 58 had α thalassaemia 1. All three HbH cases and 56 of 58 cases of a thalassaemia 1 expressed embryonic ζ chains, giving a specificity of 96.7%. Fifty four of 115 cases had a negative HbH inclusion test, of whom 50 had β thalassaemia trait and three had iron deficiency. No diagnosis was reached for the remaining patient. Conclusion - The immunocytochemical test is as sensitive as the HbH inclusion test in screening for a thalassaemia. The presence of ζ chains is highly specific for a thalassaemia I incorporating the (--/SEA) deletion. The specificity and simplicity of the immunocytochemical test make it the test of choice in screening for α thalassaemia.published_or_final_versio

Prevalence and genotypes of α- and β-thalassemia carriers in Hong Kong - Implications for population screening

Background: The thalassemias are common in southern China. We determined the prevalence of heterozygous carriers of these genetic disorders in Hong Kong and assessed the feasibility of a community-based screening program. Methods: An educational and screening program for the thalassemias was carried out in three high schools with a total of 2420 students. Seventy- five percent of the students agreed to undergo screening, which consisted of blood counts, hemoglobin electrophoresis, serum ferritin measurements, and DNA analyses. Results: Of the 1800 blood samples tested, 150 (8.3 percent) had microcytosis (mean corpuscular volume, <80 μm3). Ninety students (5.0 percent) were carriers of α-thalassemia, of whom 81 (4.5 percent) were carriers of the Southeast Asian type of deletion, in which both α-globin genes on the same chromosome 16 are deleted. Sixty-one students (3.4 percent) were carriers of either β-thalassemia or the mutation coding for hemoglobin E. Six students were carriers of both α- and β-thalassemias. On the basis of these figures, the estimated numbers of pregnancies in Hong Kong in which the fetus is at risk for homozygous α-thalassemia and β-thalassemia major or intermedia are 145 and 80 per year, respectively. In Hong Kong the actual numbers of women referred for prenatal diagnoses of these disorders are approximately 95 and 40 per year, respectively. Conclusions: Despite the availability of hospital-based screening and prenatal diagnosis for many years in Hong Kong, many women carrying fetuses at risk for thalassemia are not referred for genetic counseling. A community-based program of education, screening, and counseling is needed in Hong Kong and southern China.published_or_final_versio

Hemoglobin H disease: Not necessarily a benign disorder

Hb H disease is a form of α-thalassemia often manifested clinically as thalassemia intermedia with moderate anemia. It is commonly found in Southeast Asian, Middle Eastern, and Mediterranean populations. There is a wide spectrum of genotypes and phenotypic presentations. These range from those who appear clinically to be asymptomatic, to others who are more anemic, having significant hepatosplenomegaly and requiring occasional or even regular transfusions, to the severe Hb H hydrops fetalis syndrome that can cause death in the affected fetuses late in gestation. This hereditary disorder is usually caused by deletions removing all but one single α-globin gene (deletional Hb H disease). A small proportion of patients have deletions removing 2 α-globin genes plus a nondeletional mutation affecting a third α-globin gene (nondeletional Hb H disease). In general, nondeletional Hb H disease has a more severe clinical course than the deletional form. Review of recent literature suggests that Hb H disease is not as benign a disorder as previously thought. It can bring about growth retardation during childhood and iron overload in adults regardless of previous transfusion history, leading to hepatic, cardiac, and endocrine dysfunction. Significant anemia might occur during infections, fever, hypersplenism, or pregnancy that may necessitate the need for blood transfusions. An essential part of the maternal/child health care should include screening the partners of all pregnant women with Hb H disease for their thalassemia carrier status, and providing these and other couples who are at risk of conceiving offspring with Hb H disease with appropriate genetic counseling. Prospective and systematic studies of the natural history of Hb H disease, particularly during infancy and childhood, as well as during pregnancy, have not been carried out and are much needed. Information derived from these investigations can lead to better insight to potential risk factors associated with severe disease and can help to formulate future medical interventions and treatment strategies.link_to_subscribed_fulltex

Compound heterozygosity for triplicated α-globin gene and (- -(SEA)) α-globin gene deletion: Implication for thalassaemia screening [5]

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Routine screening of (--SEA) α-thalassemia deletion by an enzyme-linked immunosorbent assay for embryonic ζ-globin chains

We evaluated an enzyme-linked immunosorbent assay (ELISA) for embryonic ζ-globin chains as a routine screening test for (--SEA) α-thalassemia deletion (SEA deletion). A total of 174 consecutive patient samples with a request for Hb analysis were recruited. The ELISA method was evaluated against a polymerase chain reaction (PCR)-based technique that was taken as the standard. Among 56 simple carriers of SEA deletion diagnosed by PCR and 112 subjects without the SEA deletion, the sensitivity and specificity of the ELISA method was 89.3-96.4 and 98.2-100%, respectively, depending on the cutoff value for optical density that was adopted. The ELISA method was able to detect both subjects with SEA deletion and concurrent β-thalassemia trait in this series, but only 1 out of 4 patients (25%) with Hb H disease. We speculate that incomplete lysis of hypochromic microcytic red cells together with the low red cell count in Hb H disease might account for the false-negative results. We showed that the ELISA method for embryonic ζ-chains was a sensitive method of screening for SEA deletion carriers at our locality, and should be easily adopted in a routine diagnostic laboratory. The method was rapid and also amendable to automation. In areas with a high prevalence of α-thalassemia, improved detection of SEA deletion carriers would ultimately facilitate the identification of pregnancies at risk of hydrops fetalis and its prevention through prenatal diagnosis. Copyright © 2002 S. Karger AG, Basel.link_to_subscribed_fulltex

Embryonic and fetal globins are expressed in adult erythroid progenitor cells and in erythroid cell cultures

The understanding of human hemoglobin ontogeny during development is of biological and clinical importance. Molecular and immunocytological techniques were used to study the expression of embryonic zeta (ζ), epsilon (ε), and fetal gamma (γ) globin genes in newborn cord blood, peripheral blood from men, pregnant and non-pregnant women, and in vitro mononuclear cell cultures. We have shown that embryonic and fetal globin mRNA and peptides are expressed in cultured erythroid cells and in circulating blood cells from newborns, adult non-pregnant women and from men. The findings suggest that during erythroid cell differentiation in newborns and adults, there is a transient recapitulation of sequential globin chain expression as found during embryonic and fetal development. Furthermore, these findings underscore the need for caution in using embryonic and fetal globin chains as markers to identify erythroid cells of fetal origin in maternal circulation for prenatal diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.link_to_subscribed_fulltex

Haemoglobin Q-Thailand and hereditary spherocytosis in a chinese family

A Chinese family with concurrent hereditary spherocytosis (HS) and haemoglobin (Hb) Q-Thailand is described. The Hb Q-Thailand mutation was found on the remaining α1 globin gene on a chromosome 16 containing the (-α 4.2) deletion. Active haemolysis in members of this family is segregated with the HS phenotype, and the Hb Q-Thailand in the heterozygous state does not seem to show any modulating effect on HS.link_to_subscribed_fulltex

Ermap, A gene coding for a novel erythroid specific adhesion/receptor membrane protein.

Ermap (erythroid membrane-associated protein), a gene coding for a novel transmembrane protein produced exclusively in erythroid cells, is described. It is mapped to murine Chromosome 4, 57 cM distal to the centromere. The initial cDNA clone was isolated from a day 9 murine embryonic erythroid cell cDNA library. The predicted peptide sequence suggests that ERMAP is a transmembrane protein with two extracellular immunoglobulin folds, as well as a highly conserved B30.2 domain and several phosphorylation consensus sequences in the cytoplasmic region. ERMAP shares a high homology throughout the entire peptide with butyrophilin, a glycoprotein essential for milk lipid droplet formation and release. A GFP-ERMAP fusion protein was localized to the plasma membrane and cytoplasmic vesicles in transiently transfected 293T cells. Northern blot analysis and in-situ hybridization demonstrated that Ermap expression was restricted to fetal and adult erythroid tissues. ERMAP is likely a novel adhesion/receptor molecule specific for erythroid cells

β-Thalassemia intermedia caused by compound heterozygosity for Hb Malay (β codon 19 AAC→AGC; Asn→Ser) and codons 41/42 (-CTTT) β0-thalassemia mutation

We report a case of β-thalassemia intermedia caused by compound heterozygosity for hemoglobin (Hb) Malay and codon 41/42 (-CTTT) β0- thalassemia mutation in a 38-year-old Chinese woman. This patient has long- standing anemia with a baseline Hb level of around 70 g/L. She worked as a full-time cashier and had not required regular blood transfusions. Nevertheless, she had splenomegaly necessitating splenectomy, cholelithiasis, and iron overload. This case illustrates the varied phenotypic expression associated with compound heterozygosity for Hb Malay and other β-thalassemia mutations. Since Hb Malay migrates as Hb A on electrophoresis and chromatography, this variant Hb mutation ought to be included in the differential diagnosis for β-thalassemia major or intermedia patients of Southeast Asian descent who are reported to have Hb A on the basis of Hb analysis. The possible presence of this mutation should also be considered in appropriate cases for genetic counseling in couples at risk of conceiving fetuses with β-thalassemia major or intermedia. (C) 2000 Wiley-Liss, Inc.link_to_subscribed_fulltex