Preimplantation testing for phenylketonuria

Objective: To use preimplantation genetic diagnosis to achieve a phenylketo nuria-free pregnancy in a couple at 50% risk for producing an affected chil d. Design: DNA analysis of the first and second polar bodies (PB1 and PB2) obt ained from oocytes of a heterozygous mother in IVF-ET, with the goal of ide ntifying and transferring back to the patient the embryos resulting from mu tation-free oocytes. Setting: IVF program of Reproductive Genetics Institute, Chicago, Illinois. Patient(s): A mother carrying the R408W mutation and a father with compound heterozygosity for R408 and Y414C mutations in phenylalanine hydroxylase ( PAH) acne. Intervention(s): Removal and testing for maternal mutation in PB1 and PB2 f rom each oocyte after standard IVF. Main Outcome Measure(s): DNA analysis of PB1 and PB2 indicating whether cor responding oocytes were mutation-free, for the purposes of transferring onl y unaffected embryos resulting from these oocytes. Result(s): Of 11 zygotes with both PB1 and PB2, 6 were predicted to be free of phenylketonuria. Of these, 4 were transferred, resulting in an unaffect ed twin pregnancy and birth of two healthy children. Conclusion(s): Preimplantation genetic diagnosis of phenylketonuria resulte d in the. birth of phenylketonturia-free children. Preimplantation genetic diagnosis by PB analysis in couples with a compound heterozygous male partn er is clinically useful. (C) 2001 by Amexican Society for Reproductive Medi cine.