Correction of ureagenesis after gene transfer in an animal model and afterliver transplantation in humans with ornithine transcarbamylase deficiency

We report effects of gene transfer and liver transplantation on urea synthe sis in ornithine transcarbamylase deficiency (OTCD), We measured the format ion of [N-15] urea after oral administration of (NH4Cl)-N-15 in two girls w ith partial OTCD before and after liver transplantation. Ureagenesis was le ss than 20% of that observed in controls before transplantation, and was no rmalized afterward. Studies performed on the OTCD sparse fur (spf/Y) mouse showed discordance between OTC enzyme activity and ureagenesis with modest increases in OTC enzyme activity after gene transfer resulting in significa nt improvement in ureagenesis. This study suggests that both liver transpla ntation and gene therapy may be effective in improving ureagenesis in OTCD.