Background: Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap. However, the diet is very restrictive and unpalatable and can be difficult to follow. A deficiency of the amino acid tyrosine has been suggested as a cause of some of the neuropsychological problems exhibited in phenylketonuria. Therefore, this review aims to assess the efficacy of tyrosine supplementation for phenylketonuria.
Objectives: To assess the effects of tyrosine supplementation alongside or instead of a phenylalanine-restricted diet for people with phenylketonuria, who commenced on diet at diagnosis and either continued on the diet or relaxed the diet later in life. To assess the evidence that tyrosine supplementation alongside, or instead of a phenylalanine-restricted diet improves intelligence, neuropsychological performance, growth and nutritional status, mortality rate and quality of life.
Search strategy: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register which is comprised of references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional studies were identified from handsearches of the Journal of Inherited Metabolic Disease (from inception in 1978 to 1998). The manufacturers of prescribable dietary products used in the treatment of phenylketonuria were also contacted for further references.Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 09 June 2010.
Selection criteria: All randomised or quasi-randomised trials investigating the use of tyrosine supplementation versus placebo in people with phenylketonuria in addition to, or instead of, a phenylalanine-restricted diet. People treated for maternal phenylketonuria were excluded.
Data collection and analysis: Two authors independently assessed the trial eligibility, methodological quality and extracted the data.
Main results: Six trials were found, of which three trials reporting the results of a total of 56 participants, were suitable for inclusion in the review. The blood tyrosine concentrations were significantly higher in the participants receiving tyrosine supplements than those in the placebo group, mean difference 23.46 (95% confidence interval 12.87 to 34.05). No significant differences were found between any of the other outcomes measured.
Authors' conclusions: From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice. Further randomised controlled studies are required to provide more evidence.