Affiliation:
1. Department of Hematology/Oncology, Children's Hospital and Research Center, Oakland, California
2. Data Coordinating Center, New England Research Institutes, Watertown, Massachusetts
3. Department of Molecular Diagnostic Genetics, McMaster University Medical Centre, Hamilton, Ontario, Canada
4. Genetic Disease Branch, California Department of Health Services, Sacramento, California
5. Toronto General Hospital, Toronto, Ontario, Canada
Abstract
Objective. Changing patterns of immigration to North America, along with improved treatment, have altered the clinical spectrum of thalassemia, one of the world's most common genetic diseases. The new demography of the disease, with its widely variable phenotypes, has implications for its diagnosis, counseling, and management. Characterization of the new spectrum of this ancient disease, now predominated by minority groups, is essential for optimizing survival.
Methods. The National Institutes of Health–sponsored North American Thalassemia Clinical Research Network (TCRN) conducted a cross-sectional study of 721 patients with thalassemia syndromes. A detailed chart review was undertaken to define the relationships between ethnic origins, genotype, and phenotype. These results were compared with 3 previous surveys of similar regions. To determine if the TCRN patient epidemiology is representative of North American patients, 87 additional programs were reviewed, and hemoglobinopathy programs from the 2 largest thalassemia regions, Ontario and California, were analyzed.
Results. A total of 721 patients completed analysis in the TCRN study, including 389 (54%) patients with β-thalassemia major, 105 (15%) patients with β-thalassemia intermedia, 95 (13%) patients with hemoglobin E-β-thalassemia, and 132 (18%) patients with α-thalassemia. β-Thalassemia predominated in Eastern North America. Hemoglobin E-β-thalassemia and α-thalassemia were common on the Western continent. Genotype broadly correlated with the clinical phenotype. However, there was marked heterogeneity in clinical phenotype among patients with similar globin mutations. In β-thalassemia disorders, coinheritance of the α-thalassemia trait, triplication of α-thalassemia genes, and heterozygosity for the dominant β-thalassemia allele affected the clinical phenotype. In α-thalassemia disorders, structural mutations such as hemoglobin H-Constant Spring resulted in a severe hemoglobin H phenotype. Sixty percent of patients received regular transfusions, and 86% received regular iron-chelation therapy. Increased survival and decreasing birth rates of Mediterranean patients resulted in an aging Greek/Italian population being replaced by a young Asian/Middle Eastern population. Now, Asian patients account for >50% of the thalassemia population. Evidence of increasing survival is reflected in an advancing mean age of white patients with thalassemia major (25 years, up from 11 years in 1974). The results of the non-TCRN thalassemia survey confirm these observations and describe a young multiethnic thalassemia population distributed throughout North America. Newborn-screening results suggest that thalassemia births in North America are increasing and reflect the change in genotype and phenotype observed in the TCRN populations.
Conclusions. The epidemiology of thalassemia in North America reflects a heterogeneous group of diseases with new ethnicities, genotypes, and phenotypes. In these communities, physicians will need to provide education, prenatal diagnosis, counseling, and management of this newly diverse group of patients.
Publisher
American Academy of Pediatrics (AAP)
Subject
Pediatrics, Perinatology and Child Health
Cited by
98 articles.
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