Intellectual development of the patients of the German Collaborative Study of children treated for phenylketonuria

Abstract

In a multicentric and interdisciplinary approach the German Collaborative Study of Children Treated for Phenylketonuria (PKU) investigates prospectively the effects of early started strict dietary treatment on the growth and development of 140 patients. The present paper focuses on longitudinal intelligence data from 4, 5 and 9 years of age of 89 patients in relation to the quality of dietary control in comparison to 200 healthy children tested by the same protocol. Cluster analysis of phenylalanine (Phe) levels distinguished a cluster of good dietary control with Phe levels according to the recommendation of maintaining Phe levels below 360 mumol/l, a cluster of poor dietary control with Phe levels greater than 600 mumol/l after the age of 3 years, and a cluster of intermediate control. Intelligence quotients (IQ) and Phe clusters were inversely related with non-significant differences between the clusters good and intermediate. On average, all three clusters scored significantly lower than healthy age peers. Mean IQ scores decreased for patients as well as for healthy children due to different tests used at different measurement occasions. Patients with poor dietary control showed a steeper decrease between 4 and 5 years than patients with better dietary control. Between 5 and 9 years IQ differences between patients and healthy children remained stable. Verbal IQs were higher than performance IQs for patients as well as for healthy children. It is concluded that after early and strict treatment during the pre-school years Phe levels, in the range observed, do not influence IQ development until the age of 9 years. IQ subscale pattern indicate that PKU results in a generalized reduction of IQ instead of disturbing specific abilities. It remains to be investigated whether higher Phe levels are also innocuous and/or may result in late effects.

Normal Clinical Outcome in Untreated Subjects with Mild Hyperphenylalaninemia

“…534 deficits or abnormalities of cerebral white matter, as described for patients with mild or classic PKU (7)(8)(9)(10)(11)(12)(13)(14). Because of the limited accuracy of measurements, Phe levels should be taken as an approximation but not as absolute limits in every instance.…”

“…In spite of early and adequate dietary treatment, patients with mild or classic PKU show a mild reduction of IQ (7)(8)(9), abnormalities of cerebral white matter (10,11), and deficits of fine motor performances (12) and sustained and selective attention (13,14), as well as impaired executive functions depending on (pre)frontal lobe functions (15,16). The latter may be the consequence of a central dopamine depletion.…”

Diet in Phenylketonuria: How Long?

“…Authors from Heidelberg [33] concluded cautiously from their investigations: '... elevated phenylalanine levels ... resulted in a generalized moderate reduction of intelligence' and 'our results support the recommendation of a strict phenylalanine control during the first decade of life'. In another report this group [36] stated, 'Our studies favour the continuation of a strict diet at least during the first 9 years of life.…”

MAOB : un gène modificateur dans la phénylcétonurie ?

“…Il en résulte une accumulation de phénylalanine dans l'organisme, les concentrations plasmatiques pouvant être 20 à 30 fois plus élevées que la normale. Les études réalisées sur les quotients intellectuels des enfants phénylcétonuriques montrent que les enfants traités dans le premier mois de vie et de façon stricte jusqu'à l'âge de 5 ans ont des performances semblables à celles d'enfants de la population générale, mais infé-rieures d'environ 8 points à celles de leurs germains non atteints [2,3]. Donc, malgré l'instauration du traitement, certains troubles persistent, reflétant une toxicité cérébrale précoce.…”