Document Detail


Mutations in the regulatory domain of phenylalanine hydroxylase and response to tetrahydrobiopterin.
MedLine Citation:
PMID:  17627389     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lin Wang; Sankar Surendran; Kimberlee Michals-Matalon; Gita Bhatia; Susan Tanskley; Richard Koch; James Grady; Stephen K Tyring; Raymond C Stevens; Flemming Guttler; Reuben Matalon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Genetic testing     Volume:  11     ISSN:  1090-6576     ISO Abbreviation:  Genet. Test.     Publication Date:  2007  
Date Detail:
Created Date:  2007-07-13     Completed Date:  2007-09-06     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9802546     Medline TA:  Genet Test     Country:  United States    
Other Details:
Languages:  eng     Pagination:  174-8     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Amino Acid Substitution
Biopterin / analogs & derivatives*,  therapeutic use
Child
DNA Mutational Analysis
Humans
Middle Aged
Models, Molecular
Mutation*
Phenylalanine Hydroxylase / chemistry,  genetics*
Phenylketonurias / drug therapy,  enzymology,  genetics*
Protein Conformation
Regulatory Sequences, Nucleic Acid
Sequence Deletion
Grant Support
ID/Acronym/Agency:
HD023148/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; EC 1.14.16.1/Phenylalanine Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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