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
beta-thalassemia major, 105 (15%) patients with
beta-thalassemia intermedia, 95 (13%) patients with
hemoglobin E-
beta-thalassemia, and 132 (18%) patients with
alpha-thalassemia.
beta-Thalassemia predominated in Eastern North America.
Hemoglobin E-
beta-thalassemia and
alpha-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
beta-thalassemia disorders, coinheritance of the
alpha-thalassemia trait, triplication of
alpha-thalassemia genes, and heterozygosity for the dominant
beta-thalassemia allele affected the clinical phenotype. In
alpha-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.