Globin chain synthesis is heterozygous and homozygous hemoglobin E.
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Adult↗
Biomedical subjects
P Winichagoon
Publications and source records attributed to P Winichagoon.
Homozygous haemoglobin Constant Spring: a need for revision of concept.
Twenty-two patients with mild haemolytic anaemia and haemoglobin (Hb) Constant Spring (CS) of around 6% were studied because they were suspected of having homozygous Hb CS. Family studies revealed Hb CS trait in both parents of eight patients, supporting that they were homozygous for Hb CS. The other patients were included because they had clinical and haematological features similar to the diagnosed cases of homozygous Hb CS. Heterozygosity and homozygosity for Hb CS are clearly distinguishable in that the former is asymptomatic but the latter is associated with overt haemolytic anaemia, and the levels of Hb CS in the two conditions of less than 1% and around 6%, respectively, do not overlap. The findings in homozygous Hb CS contradict prediction. There are four alpha-structural genes per normal human diploid genome. Hb CS trait is believed to be almost equivalent to alpha-thalassaemia 2 or a loss of one alpha-gene because HB CS, and alpha-variant, is barely or not detectable. Homozygosity for Hb CS has thus been predicted to be equivalent to alpha-thalassaemia 1 or a loss of two genes. The latter is asymptomatic and associated with microcytic-hypochromic red cells. However, Hb CS homozygosity presents with mild overt haemolytic anaemia and normal sized red cells. Pathogenesis associated with Hb CS inheritance is more complex than originally believed. There is a possibility that the unstable alpha CS mRNAs precipitate and aggregate leading to pathology of red cells and to the basophilic stippling appearance, so striking in this syndrome.
Adolescent↗
Increased circulating platelet aggregates in thalassaemia.
Examination for circulating platelet aggregates according to Wu and Hoak revealed increased circulating platelet aggregates in 71% of splenectomized and 35% of nonsplenectomized patients with beta (0)-thalassaemia/Hb E disease. This may be causally related to the newly observed high incidences of pulmonary artery thrombosis and hypoxaemia in splenectomized thalassaemic patients. It is recommended that anti-platelet aggregation drugs such as aspirin and/or dipyridamole are given to thalassaemic patients after splenectomy.
Humans↗
Immunologic diagnosis of alpha-thalassemia traits.
Frequently it is impossible to diagnose alpha-thalassemia-2 trait from hematologic findings, since the red cell morphology and the MCV are normal. In such cases, after the neonatal period Hb Bart's is not detectable by conventional electrophoreses and chromatography. Antibody against Hb Bart's was produced in rabbits by repeated injections with Hb Bart's from Hb Bart's hydropic fetuses. The antibody was specific for Hb Bart's without crossreaction with Hbs A, A2, E, F and H. By the capillary tube precipitin test Hb Bart's was demonstrable in 82% of 87 obligatory cases for alpha-thalassemia traits, 86% in alpha-thalassemia-1 trait and 79% in alpha-thalassemia-2 trait. The test was positive in 21% of the general subjects, corresponding to the prevalence of alpha-thalassemia in Bangkok. Thus the immunologic demonstration of Hb Bart's appears to offer a diagnostic screening test for alpha-thalassemia traits in the postneonatal period.
Animals↗
The molecular basis of thalassemias.
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Humans↗
Genetic factors affecting clinical severity in beta-thalassemia syndromes.
PURPOSE: Heterogeneity in the clinical manifestation of beta-thalassemic diseases may occur from the nature of beta-globin gene mutations, alpha-thalassemia gene interaction, or differences in the amount of hemoglobin (Hb) F production. This study was conducted to determine whether these genetic determinant factors can predict phenotypic severity of patients with beta-thalassemia and to assess the relationship between the genotype and phenotype of the disease. MATERIALS AND METHODS: A total of 144 patients with beta-thalassemia were divided into mild (46 patients), intermediate (55 patients), and severe groups (43 patients). DNA analysis based on polymerase chain reaction technique was performed to characterize types of beta-thalassemia mutation, interaction of alpha-thalassemia, and XmnI polymorphism 5' to Ggamma-globin gene. RESULTS: Two alleles of mild beta-thalassemia mutation (beta+/beta+-thalassemia or beta+-thalassemia/Hb E) resulted in a mild clinical symptom whereas two alleles of severe beta-thalassemia mutation (betao/betao) produced a severe clinical phenotype. Compound heterozygosity for mild and severe alleles of beta-thalassemia (betao/ beta+-thalassemia or betao-thalassemia/Hb E) led to variable severity of anemia. Coinheritance of alpha-thalassemia alleviated the severity of beta-thalassemia disease in those patients with at least one allele of the mild beta-thalassemia genotype. DNA polymorphism at position-158 nt 5' to the Ggamma-globin gene was demonstrated by XmnI restriction enzyme. Homozygote of the XmnI site, +/+, was found to have a strong linkage with high Hb F levels and high hemoglobin production in two patients who had mild clinical symptoms. However, some patients who had XmnI site -/- also had mild clinical symptoms because the XmnI- was found to be associated with beta+-thalassemia mutation. CONCLUSION: Types of beta-thalassemia mutation and coinheritance of alpha-thalassemia in the patient who has at least one allele of the mild beta-thalassemia genotype are predictive for the clinical severity of the disease. However, a mild clinical symptom in some patients with betao/beta+-thalassemia or betao-thalassemia/Hb E who do not have a detectable alpha-thalassemia haplotype and no linkage with XmnI++ suggests that there are other confounding factors responsible for the severity differences of the disease.
Age of Onset↗