Phenylketonuria: questioning the gospel

Abstract

Phenylketonuria (PKU) was first described over 70 years ago, treatment was developed 50 years ago and universal newborn PKU screening was introduced 40 years ago. Phenylalanine-restricted dietary treatment has prevented mental retardation in thousands of individuals worldwide. We acknowledge, however, that there is still much to learn in the field. The incidence of mental retardation in untreated PKU is likely to be considerably less than the original estimates. Since dietary control is suboptimal in late childhood, adolescence and adulthood, alternative methods of treatment are being explored. These include large neutral amino acids, phenylalanine ammonia lyase, tetrahydrobiopterin and gene replacement. Evidence has surfaced that the semisynthetic, low-protein diet used to treat PKU may be deficient in certain important nutrients. Maternal PKU treatment may be successful even if initiated as late as 8–10 weeks into pregnancy. A plea is made for the immediate establishment of adult treatment centers for PKU (and other inherited metabolic diseases) for long-term treatment, follow-up and research.

Keywords::

• hyperphenylalaninemia
• large neutral amino acids
• maternal phenylketonuria
• non-PKU mild hyperphenylalaninemia
• phenylalanine
• phenylalanine ammonia lyase
• phenylalanine hydroxylase
• phenylketonuria
• proton nuclear magnetic resonance spectroscopy
• tetrahydrobiopterin

Acknowledgements

WB Hanley would like to thank JTR Clark for advice and support.

Financial & competing interests disclosure

Supported by a grant from the Maranatha Foundation, Toronto, Canada. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.