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 mumol/l (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.

Diet in Phenylketonuria: How Long?

“…It is amazing to note that the authors concluded that these abnormalities had nothing to do with early diet discontinuation. Similar results from patients whose diet had been relaxed at 5 years of age were reported by the same group 9 years later [6].…”

Management of Phenylketonuria for Optimal Outcome: A Review of Guidelines for Phenylketonuria Management and a Report of Surveys of Parents, Patients, and Clinic Directors

“…Many reports have shown that optimum outcome occurs when dietary therapy is started early and continued indefinitely. 22,[25][26][27][28][29][30][31][32][33][34][35][36] As with other chronic illnesses, decreased compliance and poor dietary control increase with age, especially after 6 years of age. 17,25,37,38 Older individuals who have discontinued dietary therapy are at risk for developing loss of intelligence, magnetic resonance imaging findings consistent with white matter dysfunction, and occasionally acute demyelinating neuropathies.…”

Función neuropsicológica en la fenilcetonuria tratada precozmente: Una revisión

“…En contraste, aunque los pacientes tratados precozmente se presentan habitualmente con una función intelectual dentro del margen normal [7,31,[39][40][41] , a menudo generan puntuaciones menores en comparación con controles familiares indemnes [42,43] y controles indemnes ajenos a la familia [44] .…”

“…Los informes de tasas elevadas de niños con FCU que acuden a entornos de educación especial [42,77,78] parecen limitarse a estudios en los que participaron pacientes nacidos antes de la década de los 80, época en la que el tratamiento dietético era más laxo. No obstante, se dispone de datos a favor de que niños con FCU tratados precozmente que acuden a entornos escolares normales rinden todavía menos que los controles.…”