ORC1 and Hyperornithinemia: Defective ORC1 reduces the rate of the urea cycle, leading to hyperammonemia and to the build-up of ornithine in the cytosol, which causes hyperornithinemia, increased levels of polyamines and a secondary creatine deficiency (due to an inhibition of arginine-glycine amidotransferase (AGAT) by an excess of ornithine).