Urea cycle disorders are incurable enzyme defects that affect nitrogen metabolism and typically lead to elevated nitrogen. Arginase deficiency results from a mutation in the arginase 1 gene, typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, with some being treated by liver transplantation which is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for cell transplantation. In this study, we demonstrate a universally-applicable gene editing strategy utilizing the hypoxanthine-guanine phosphoribosyltransferase gene to genetically modify and restore arginase activity in genetically distinct patient-specific human induced pluripotent stem cells and liver cell derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism.