A retrospective analysis of synthetic protein prescription in Irish children with phenylketonuria

Abstract

Background: Phenylketonuria (PKU) is an inherited inborn error of metabolism resulting in the inability of the patient to metabolise the essential amino acid (AA) phenylalanine (Phe) and convert it to tyrosine. Untreated, a build-up of Phe occurs that damages the brain and leads to mental retardation (Williams et al., 2008). Management guidelines for the treatment of the disorder by the Medical Research Council (MRC) make recommendations on the quantity of AA substitute to be provided and the desired ranges for Phe levels. The aim of this study was to address the hypothesis that children consuming less than recommendation for synthetic AA intake can grow normally and achieve good biochemical control. Methods: Patients with moderate to classical hyperphenylalaninaemia born between the 1 January 1998 and December 2008 were retrospectively identified from the patient database of the National Centre for Inherited Metabolic Disorders for inclusion in the study. Anthropometric data and protein intake data were collected from medical records of 121 patients from birth to the age of 2 years, at six specific time-points. From these data, exact weight/height centiles and change in centile z-scores were calculated. Intakes (g kg−1) of synthetic AAs and natural protein were calculated at each time-point based on protein intake reported by parents and noted in dietetic notes. The cohort was split into groups based on synthetic AA intake: ≥ 3g kg−1day−1, representing those meeting the MRC guidelines, 1.5–1.99 g kg−1 day−1 and 2–2.5 g kg−1 day−1. These groups were then statistically compared in terms of growth parameters and biochemical control using Student's t-tests and Mann–Whitney U-tests depending on data distribution. Results: At 2 years, subjects in the groups achieving lower than the recommended synthetic AA intake displayed a significantly smaller decrease in the change in z-score for height (P = 0.001 for 2–2.5 g kg−1 group, P = 0.034 for 1.5–1.99g kg−1 group compared to ≥3 g kg−1 day−1) and weight (P = 0.006 for 2–2.5 g kg−1 group compared to ≥3 g kg−1 day−1), indicating that they had less of a growth deficit compared to those meeting the AA intake guideline. Mean blood Phe levels over the time-points investigated were also significantly lower in the groups consuming less than the MRC guideline. Discussion: This study has shown that the growth deficit is less in patients consuming decreased amounts of synthetic protein. Schaefer et al. (1994) found no correlation between Phe intake and the rates of growth, although they did not analyse the effect of synthetic protein intake on these parameters. In the current study, significant negative correlations were found between change in weight and height centile z-scores and synthetic AA intake at 2 years. This negative correlation was upheld, even when the confounding effect of natural protein intake was controlled for. These results are contrary to previously published studies showing no correlation between protein intake and growth retardation (Weglage et al., 1994; Dobbelaere et al., 2003). As with the study by Schaefer et al. (1994), these studies did not analyse the two separate fractions of protein that PKU patients consume (i.e. natural and synthetic). These results support the hypothesis that children can achieve adequate growth and biochemical control at synthetic AA intakes below the MRC recommendation. Conclusions: This study provides a base upon which prospective studies should be designed to determine a more appropriate synthetic AA intake recommendation for children with PKU.