Mutations in the regulatory domain of phenylalanine hydroxylase and response to tetrahydrobiopterin.
Tetrahydrobiopterin (BH4) is a co-factor that enhances the activity of other enzymes, and this co-factor level is found to be affected in phenylketonuria (PKU), an amino acid metabolism disorder. The present study was aimed at understanding the effect of BH4 on mutations in the regulatory domain of phenylalanine hydroxylase (PAH). Among 14 patients, 5 patients were classical PKU, 3 were atypical PKU, and 6 were mild PKU. All of these patients had at least one mutation in the regulatory domain. Patients were given 10 mg/kg BH4, and the response of blood phenylalanine (Phe) levels was monitored following treatment. The level of blood Phe decreased after BH4 treatment in all of the patients. These studies suggest that mutations in the regulatory domain also responded to BH4 even if the patient had classical PKU.
Wang
Lin
L
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Surendran
Sankar
S
Michals-Matalon
Kimberlee
K
Bhatia
Gita
G
Tanskley
Susan
S
Koch
Richard
R
Grady
James
J
Tyring
Stephen K
SK
Stevens
Raymond C
RC
Guttler
Flemming
F
Matalon
Reuben
R
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000737:chemistry / Q000235:genetics*; D010661:Phenylketonurias / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D011487:Protein Conformation; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion
D001708:Biopterins; D010651:Phenylalanine Hydroxylase; C003402:sapropterin