Phenylketonuria is an autosomal recessive inborn error of phenylalanine metabolism due to the lack of phenylalanine (phe) hydroxylase enzymatic activity. The different clinical forms are correlated to the variable levelof residual enzyme activity, to the plasma phe levels and to the occurrence of urinary ketones excretion. A further and more severe form of phenylketonuria is caused by the lack of tetrahydrobioterin, the cofactor of phenylalanine-, tyrosine- and tryptophan-hydroxylase. The major clinical feature is represented by progressive mental retardation likely linked to toxic effects of high plasma phe levels on the nervous system. The early appearance of biochemical abnormalities makes the newborn screening test feasible and necessary for early introduction of the adequate therapy. This is currently based on a low-phe diet in order both to prevent the neurological damage by maintaining plasma phe within a safety range and to ensure an adequate intake of essential amino-acids for growth. The diet is constituted by particular low-phe formulas, very few animal protein and mostly vegetal foods and fruits and caloric supplementations (mainly vegetal oils). It should be continued for life, in order to avoid both late mental damages occurring in children and aldults after diet interruption and the embryofetopathic effects of high plasma phe levels in pregnant PKU women (maternal PKU). The nutritional consequences of such a 'lacking-diet', derived from the low intake of the so called 'conditionally essential compounds' (i.e. carnitine, taurine, trace elements and very long-chain polyunsaturated fatty acids) in classical PKU patients on diet as well as in pregnant PKY women in the current main problem concerning phenylketonuria
