The Neurotoxic Metabolite of Phenylalanine in Phenylketonuria

L-Arginine and calcium pantothenate significantly lowered plasma phenylalanine levels, dramatically reduced phenylacetate production, and counteracted the myelin deficit in the young suckling rat in which sustained hyperphenylalaninemia was induced. In experimental maternal hyperphenylalaninemia, offspring of mothers fed a semisynthetic diet displayed microcephaly, a deviant ganglioside pattern, and a significant deficit of sialoglycoproteins in the cerebral hemispheres. These noxious effects were prevented by replacing the semisynthetic diet with a protein diet that provided bound sialic acid, aminohexoses, N-acetylated aminohexoses in skim milk powder, and supplements of L-arginine, calcium pantothenate, and D-glucosamine.