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What we know that could influence future treatment of phenylketonuria

  • BH4 and PKU
  • Published:
Journal of Inherited Metabolic Disease

Summary

Phenylketonuria (PKU), a Mendelian autosomal recessive phenotype (OMIM 261600), is an inborn error of metabolism that can result in impaired postnatal cognitive development. The phenotypic outcome is multifactorial in origin, based both in nature, the mutations in the gene encoding the l-phenylalanine hydroxylase enzyme, and nurture, the nutritional experience introducing l-phenylalanine into the diet. The PKU story contains many messages including a framework to appreciate the complexity of this disease where phenotype reflects both locus-specific and genomic components. This knowledge is now being applied in the development of patient-specific therapies.

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Abbreviations

PKU:

phenylketonuria

PAH :

phenylalanine hydroxylase gene

PAH:

phenylalanine hydroxylase

Phe:

phenylalanine

Tyr:

tyrosine

HPA:

hyperphenylalaninaemia

LSDB:

locus-specific database

PAHdb:

phenylalanine hydroxylase locus-specific mutation database

BH4 :

(6R)-l-erythro-5,6,7,8-tetrahydrobiopterin

LNAA:

large neutral amino acids

PAL:

phenylalanine ammonia lyase

PEG:

polyethylene glycol

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Acknowledgements

The authors thank Dr. Raymond C. Stevens and BioMarin Pharmaceutical Inc. for making this work possible.

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Authors and Affiliations

  1. Departments of Biology, Human Genetics and Pediatrics, McGill University, Montreal, Quebec, Canada

    C. N. Sarkissian & C. R. Scriver

  2. DeBelle Laboratory for Biochemical Genetics, Montreal Children’s Hospital Research Institute, 2300 Tupper Street, Rm. A-724, Montreal, Quebec, Canada, H3H 1P3

    C. N. Sarkissian & C. R. Scriver

  3. Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1 Laboratorio 204. Campus Cantoblanco, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain

    A. Gámez

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  1. C. N. Sarkissian
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Correspondence to C. N. Sarkissian.

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Communicating editor: Nenad Blau

Competing interests: None declared

References to electronic databases: Phenylketonuria: OMIM +261600. Phenylalanine hydroxylase: EC 1.14.16.1. Phenylalanine ammonia lyase: EC 4.3.1.5. PAHdb, Phenylalanine hydroxylase locus-specific mutation database: www.pahdb.mcgill.ca. GeneReviews: www.genereviews.org.

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Sarkissian, C.N., Gámez, A. & Scriver, C.R. What we know that could influence future treatment of phenylketonuria. J Inherit Metab Dis 32, 3–9 (2009). https://doi.org/10.1007/s10545-008-0917-7

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