PURPOSE: To review the clinical manifestation and changes in hematologic parameters of patients with beta-thalassemia/hemoglobin (Hb) E. MATERIALS AND METHODS: Retrospective analysis of the clinical manifestation of 378 patients with beta-thalassemia/Hb E attending the hematology clinic at Siriraj Hospital between 1957 and 1982. RESULTS: A wide spectrum of clinical phenotypes has been observed. Most patients show clinical symptoms by 10 years of age. The majority of patients survive with or without occasional transfusion. Splenectomy was performed in 26.5% of patients. Patients come to the hospital because of anemia, fever, abdominal mass, and jaundice. Gastrointestinal tract disturbances are the most common presenting symptoms (34.6%), especially abdominal pain (10%) and cholecystitis (5.1%). Respiratory tract infections were found in 21.8% of patients and cardiovascular complications, including congestive heart failure, occurred in 11.9%. Other less common symptoms and complications included bone pain, chronic leg ulcers, paraplegia and hypertension-associated convulsions, and cerebral hemorrhage after multiple blood transfusion. Patients usually die between 20 to 40 years of age (67%), mainly from congestive heart failure and septicemia. Septicemia was often caused by Gram-negative bacteria. CONCLUSION: These clinical features observed in patients with beta-thalassemia/Hb E are probably the results of chronic anemia and iron overload. The study of the life history and clinical courses of patients with beta-thalassemia/Hb E should provide important information for the better management of these patients.

Adult↗

PubMedDate not supplied

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↗