IMPLICATIONS OF GENOTYPING OF SPOUSES TO LIMIT INVESTIGATION OF CHILDREN IN GENETIC HEMOCHROMATOSIS

Background: A genetic test for hemochromatosis has allowed for the fir st time, genotypic identification of heterozygotes. The purpose of thi s study is to determine whether genotyping of spouses of homozygotes r esults in fewer investigations of children and subsequent cost savings . Methods: Two hundred and ninety one children of homozygotes were stu died using HLA typing, transferrin saturation and serum ferritin. Nine ty six percent of the probands were homozygous for the C282Y mutation of the HFE gene. Pedigrees were reviewed to determine cost savings inc urred if the spouse had been genotyped to guide follow-up studies in t he children. Paternity was confirmed by HLA studies. Results: There we re 13 homozygotes identified. All homozygous children tested (10/10) w ere homozygous for the C282Y mutation. There were no iron loaded child ren identified in homozygotes negative for the C282Y mutation. Genotyp ing of the spouse eliminated the need for the investigation of 269 chi ldren. The cost savings of this strategy were modeled using the cost o f the family studies (consultation, iron studies) minus the cost of sp ouse assessment (consultation, genotyping) plus the cost of assessment of children in families in which the spouse was a heterozygote, The s pousal genotyping strategy resulted in a cost savings of 39%. Conclusi on: Genotying the spouse of a homozygote is the best cost-efficient st rategy in pedigree studies because it leads to more selective investig ation of children for the hemochromatosis gene.