Background

Phenylketonuria is an inherited disease characterised by an absence or deficiency of the enzyme phenylalanine hydroxylase. The aim of treatment is to lower blood phenylalanine concentrations to prevent developmental delay. Current treatment is based on a low phenylalanine diet in combination with a protein substitute (mixtures of amino acids free from or low in phenylalanine). Guidance regarding the dosage and distribution of this protein substitute, over a 24‐hour period, is unclear and there is variation in recommendation between treatment centres.

Objectives

To assess in children and adults with phenylketonuria, who are adhering to a low phenylalanine diet, the benefits and adverse effects of protein substitute, its dosage and distribution of dose.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted manufacturers of the phenylalanine‐free and low phenylalanine protein substitutes for any data from published and unpublished randomised controlled trials.

Date of the most recent search of the Group's Trials Register: May 2006.

Selection criteria

All randomised or quasi‐randomised controlled trials comparing: any dose of protein substitute with no protein substitute; an alternative dosage; or the same dose, but given as frequent small doses throughout the day compared with the same total daily dose given as larger boluses less frequently.

Data collection and analysis

Both authors independently extracted data and assessed trial quality.

Main results

The searches identified 25 trials, of which one, including a total of 28 participants, was eligible for inclusion in the review. This was a two‐phase trial, with only phase one being a randomised controlled trial. As data from both phases were combined in the analysis presented in the published paper, we are currently unable to include any data from the randomised controlled trial in the analysis of this review.

Authors' conclusions

No conclusions could be made about the short‐ or long‐term use of protein substitute in phenylketonuria due to the lack of adequate trial data. A randomised controlled trial is needed to investigate the use of protein substitute in phenylketonuria. Until further evidence is available current practice in the use of protein substitute should continue to be observed and monitored with care.