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 PKU. Therefore, this review aims to assess the efficasy of tyrosine supplementation for phenylketonuria.
Objectives: To assess the effects of tyrosine supplementation alongside or instead of phenylalanine restricted diet for patients 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 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 Trials Register which is a specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Additional studies were identified from handsearching the Journal of Inherited Metabolic Disease (from inception, 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 specialised register: November 1999.
Selection criteria: All randomised or pseudo-randomised trials investigating the use of tyrosine supplementation versus placebo in patients with phenylketonuria in addition to, or instead of, a phenylalanine restricted diet. Patients treated for maternal phenylketonuria were excluded.
Data collection and analysis: Two reviewers independently assessed the trial eligibility, methodological quality and extracted the data.
Main results: Two trials were included with a total of 47 patients. The blood tyrosine concentrations were significantly higher in the patients receiving tyrosine supplements than those in the placebo group (weighted mean difference 22.526, 95% Confidence interval (CI) 12.182 - 32.870). No significant differences were found between any of the other outcomes measured.
Reviewer's 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 further evidence.