Document Detail


Future treatment strategies in phenylketonuria.
MedLine Citation:
PMID:  20123478     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phenylketonuria (PKU) was the first inherited metabolic disease in which treatment was found to prevent clinical features of the disorder; dietary management was established almost 60 years ago. The institution of a low-phenylalanine (Phe) diet in the first few weeks of life was made possible by Guthrie neonatal screening, which further increased effectiveness of therapy. Indeed, neonatal diagnosis of PKU followed by institution of a low-Phe diet has been a remarkable success in preventing the devastating brain damage associated with untreated PKU. Nevertheless, significant difficulties exist in caring for PKU patients, including problems with adhering to the prescribed dietary regimen and the presence of neurocognitive deficits despite therapy. During the past few years, several ideas for new treatment strategies have emerged. This review aims to address these treatment strategies based on theoretical considerations of the biochemistry and pathogenesis of PKU. Recent times have seen the introduction of a wide array of novel treatments currently in clinical use, including more palatable medical foods, glycomacropeptide, large neutral amino acids, and tetrahydrobiopterin. Human trials are underway using an enzymatic therapeutic approach, while preclinical work continues in the fields of gene and cellular therapy. These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU.
Authors:
Francjan J van Spronsen; Gregory M Enns
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  99 Suppl 1     ISSN:  1096-7206     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2010  
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-06-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S90-5     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Affiliation:
Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Centre of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands. f.j.van.spronsen@bkk.umcq.nl
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MeSH Terms
Descriptor/Qualifier:
Blood-Brain Barrier
Humans
Patient Compliance
Phenylalanine / pharmacokinetics
Phenylketonurias / diet therapy*
Chemical
Reg. No./Substance:
63-91-2/Phenylalanine

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