Dietary Treatment of PKU : Metabolic and Nutritional Implications

Hyperphenylalaninemia (HPA) is an inborn error of phenylalanine metabolism, due to the deficiency of phenylalanine hydroxilase, which leads to the increase of phenylalanine and its metabolites in plasma, urine and central nervous system, with developmental delay. Only 2% of cases is due to tetrahydrobiopterin deficiency. The only therapy at present at our disposal is a diet-therapy characterized by natural nutrients (like fruit and vegetables) and phenylalanine-free protein products together with aminoacids powder. The diet therapy has to be started as soon as possible and has to be followed all life long. Since the first attempt to treat a PKU patient with a low-Phe diet, new challanges in the management of PKU have to be considered: optimal growth, optimal nutritional status, optimal compliance and quality of life of the patients. PKU subjects need special attention in the definition of optimal supplementation of nutrients, which may be insufficient in relation to the type of diet and may otherwise manifest symptoms of deficit. In particular, it is necessary to pay great attention to the long-chain polyunsaturated fatty acid (LC-PUFA) levels in relation to correct development of the central nervous system. On the basis of numerous beneficial effects currently known, a permanent supplementation with LC-PUFA, in particular with docosahexaenoic acid, should be considered. Moreover, new formulas, Phe-free peptides, and "modulated" amino acid preparations might help in preventing nutritional dificiencies and imbalances, with the ultimate aim of improving growth. New strategies-such as supply of tetrahydrobiopterin- need to be optimized in terms of targets, patients and expected outcomes.