The thalassemias among Laotians, Chinese and Filipinos in Hawaii : prevalences, gene frequencies, geographic distributions, screening strategy

Thesis (Ph. D.)--University of Hawaii at Manoa, 1991.Includes bibliographical references (leaves 192-206)Microfiche.xi, 206 leaves, bound ill.,maps 29 cmBoth alpha and beta thalassemias and hemoglobin E structural variants are examined in three ethnic groups now residing in Hawaii: Chinese, Laotian and Filipino (N=2644). The purpose of this dissertation was; (I) to estimate prevalences and gene frequencies in the Hawaii sample, and to look at geographic distributions of the thalassemias within the original countries of these immigrants; and (II) to use red blood cell indices phenotypes to determine the possibility of developing new algorithms which would distinguish between normals and thalassemias, and between single, double and triple deletion alpha thalassemias with clinically acceptable rates of accuracy. High prevalences of singly and concomitantly inherited thalassemias (compound heterozygotes) were found in the Hawaii sample (Laotians 58.9%; Chinese 33.8%, Filipinos 40.5%) . Gene frequencies, corrected for bias, were estimated. Gene frequencies within Laos, the Philippines and China were estimated and mapped according to geographic region of family origin. In order to detect the thalassemias, red cell indices from the complete blood count generated by electronic particle counter were analyzed and yielded the algorithm l/(l+e^-L ) where L is the intercept constant -149.9 plus (RBCount constant 2.27 * RBCount measured) + (Hglobin constant -2.97 * Hglobin measured) + (Hcrit constant 0.72 * Hcrit measured) + (MCV constant 1.40 * MCV measured) + (MCH constant -5.10 * MCH measured) + (MCHConc constant 5.20 * MCHConc measured) . This algorithm identified normals and abnormals (thalassemias) with 92.3% accuracy. After thalassemia is indicated by the algorithm, the results of hemoglobin A2 measurement clearly delineate those with beta thalassemias and heterozygous and homozygous Hb E. A second discriminant algorithm was derived which distinguishes single, double and triple deletion alpha thalassemias with 94.6% accuracy. Inheritance of more than one form of thalassemia (concomitant inheritance or compound heterozygosity) may confound results. Both algorithms are relatively simple and can be readily applied by calculator; simple programming of microcomputers provides immediate results upon entry of the complete blood count indices. Inclusion of these two algorithms as steps in genetic screening strategies for the thalassemias may enhance effectiveness by more accurately targeting individuals at risk and providing presumptive diagnoses which will be of particular value where DNA analysis is not available