Long-term follow up of patients with classical phenylketonuria after diet relaxation at 5 years of age

Abstract

The age for discontinuing dietary treatment of phenylketonuria (PKU) has been a worldwide source of controversy for many years. It is the reason we report here the results of a prospective, controlled study in which the diet was relaxed at 5 years of age in 31 so far well-treated children with classical PKU. The increase of phenylalanine (Phe) plasma levels to about 1500 µmol/1 (25 mg/dl) after relaxing the diet was not associated with any significant decline of intellectual performance as measured by the Wechsler scores. Paired comparisons at 7–8 years and 11–13 years of age (n=12) have shown WISC scores of 102.6±16.2 and 104.8±16, respectively, which were not significantly different. Similarly, paired comparisons at 9–10 years and 14–16 years (n=6) did not demonstrate a significant loss of IQ points (107.7±13 vs 104.8±18). Of course, it is possible to argue that we should have observed an increase in IQ with increasing age in our patients and that the absence of deterioration cannot be considered by itself as a good result. Nevertheless, it cannot be excluded that the subtle but global intellectual impairments that have been documented in early-treated subjects are, to a very substantial degree, determined in the pre-school years, long before there is any question of stopping or relaxing the diet.