Phenylketonuria: nutritional advances and challenges

Marcello Giovannini,Elvira Verduci,Elisabetta Salvatici,Sabrina Paci,Enrica Riva

doi:10.1186/1743-7075-9-7

Marcello Giovannini, Elvira Verduci + Show 3 more

Open Access

https://doi.org/10.1186/1743-7075-9-7

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Journal: Nutrition & Metabolism	Publication Date: Feb 3, 2012
Citations: 106	License type: cc-by

Affiliation: Ospedale San Paolo, University of Milan

Abstract

Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed.In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients.

Highlights

Since the first attempt to treat a patient affected by phenylketonuria (PKU) with a low phenylalanine (Phe) diet, many steps forward have been made in the treatment of PKU
Treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment
In PKU severe neurological and functional disorders can be prevented through an early strict nutritional treatment aimed at reducing blood Phe to non-toxic levels through a PKU diet

Summary

Introduction

Since the first attempt to treat a patient affected by phenylketonuria (PKU) with a low phenylalanine (Phe) diet, many steps forward have been made in the treatment of PKU. Poorer school performance of PKU children was reported, with significantly lower academic performance, initiative and progress than in age matched omnivorous children [6] These subtle functional deficits in early and well treated individuals with PKU are not explained by variations in plasma Phe levels, and it is plausible that a low DHA supply induced by the extremely restricted diet contributes to neurological abnormalities. Studies in the PKU mouse model demonstrate that GMP supplemented with limiting indispensable amino acids (tyrosine and tryptophan) provides a nutritionally adequate source of protein and improves the metabolic phenotype by reducing concentrations of Phe in plasma and brain [29]. In conclusion oral PAL therapy could be an adjunct therapy, perhaps with dietary treatment, independently from the PAH genotype

Conclusion

Findings

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