Phenylketonuria: tyrosine beyond the phenylalanine-restricted diet.
Controversies exist on the role of tyrosine in the pathogenesis of phenylketonuria (PKU) and, consequently, on the therapeutic role of tyrosine. This review examines data and theoretical considerations on the role of tyrosine in the pathogenesis and treatment of PKU. It is concluded that treatment with tyrosine alone to replace the phenylalanine-restricted diet cannot be justified. A treatment with large neutral amino acids (LNAA) including tyrosine to restore the balance in the transport of phenylalanine and other LNAA across the blood-brain barrier deserves further investigation. Such studies should prove the safety and the efficacy of such a treatment, finding the optimal dose of all LNAA, disclosing the correct age to start and the way to monitor treatment biochemically.
van Spronsen
F J
FJ
Department of Metabolic Diseases, Beatrix Children's Hospital, University Hospital of Groningen, The Netherlands. f.j.van.spronsen@bkk.azg.nl
Smit
P G
PG
Koch
R
R
D021542:Amino Acids, Neutral / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D006801:Humans; D018377:Neurotransmitter Agents / Q000096:biosynthesis; D010649:Phenylalanine / Q000008:administration & dosage; D010661:Phenylketonurias / Q000178:diet therapy / Q000188:drug therapy* / Q000209:etiology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D014443:Tyrosine / Q000502:physiology* / Q000627:therapeutic use*
D021542:Amino Acids, Neutral; D018377:Neurotransmitter Agents; D014443:Tyrosine; D010649:Phenylalanine