Growth and skeletal maturation was evaluated in 82 children participating in the German Collaborative Study of Children Treated for Phenylketonuria (PKU). Height, weight, head circumference and bone age were recorded at regular intervals for the first 6 years of life. The mean SD score (SDS) for height was not significantly different from zero at study entry, but decreased mainly during the second year of life to a nadir of -0.78 in boys and -0.54 in girls at 2.5 years. During the subsequent years, a significant trend towards a regain of height SDS was noted in both sexes. Weight-for-height SDS was close to zero in both sexes, with a significant continuous increasing trend throughout the observation period. Head circumference SDS decreased in boys during the first year of life from -0.28 to -0.68, whereas girls showed only a minor change. During the further follow-up period, head circumference SDS remained at approximately -0.3 in boys and 0.0 in girls. While the mean verbal and performance IQ of the total study population at 5 and 6 years of age did not differ from a group of 212 healthy non-PKU children, patients with a head circumference SDS less than the population median at 2 years of age exhibited poorer cognitive abilities at school age than those patients with a relative head size greater than the population median. The children with a head circumference less than the median at 2 years had smaller head sizes already at birth; in addition, the change in relative head size during the first 2 years was correlated significantly with cognitive abilities at school age in boys. Mean bone age was identical to chronological age at each time point of observation. The rate of maturation was one year of bone age per year of chronological age. No correlation between phenylalanine intake or phenylalanine concentrations and the rates of body or head growth or skeletal maturation could be established. We conclude that despite adequate weight gain, moderate growth retardation occurred during the first 2 years of life in this group of children treated for PKU. Growth was more compromised in boys than in girls and tended to be compensated during later follow-up. Early infantile head circumference and growth appear to be predictors of cognitive development.

A series of information processing tasks was administered to 22 PKU children aged 8.5 years who had been under dietary treatment since birth as well as to 20 controls of the same age. This contribution presents the results of two tasks from this series: a continuous performance task and a calculation task. The continuous performance task revealed a sustained attention deficit in the PKU group. In the calculation task the PKU children were slower than the controls and this difference increased with task difficulty. When the PKU sample was divided in two groups (above and below the median value of the concurrent plasma Phe level), the high Phe level group performed much worse in comparison to the low Phe level group. The latter group actually matched performance level of the controls. This could be observed for both tasks. The serum Phe level, assessed since birth over 6 month periods, correlated highly with task performance. As regards sustained attention, the Phe level measured during the 2 years preceeding test administration appeared to be an even better predictor for task performance than the concurrent Phe level, a finding which seems to underline the chronic effect of Phe on basic attention mechanisms. The results so far seem to stress the value of well-controlled dietary restrictions.

A West German multicentre study (eight centres) of PKU was designed in 1976. The subjects of the study are the differential diagnosis, factors influencing the therapeutic outcome, and the extension of dietary therapy into adolescence. Between 1978 and 1984, 165 patients were enrolled, of whom 38 were of non-German nationality. The educational and occupational status of the West German parents were comparable to the population of the Federal Republic of Germany. In the central data bank located at the University Childrens Hospital in Heidelberg, data from recurrent medical examinations and from biochemistry, dietetics, neurology, psychometry and demography were collected. The differential diagnosis of the elevated plasma Phe level in the newborn period resulted in the detection of 2 patients with a PTPS-deficiency, and of 163 with an apo-enzyme defect. Depending upon the magnitude of the Phe levels during the first weeks of life, preliminary treatment groups were formed. They were revised at the age of 6 months with a protein challenge. The levels of Phe during the protein challenge resulted in three types of response. Of these, type III can apparently forgo dietary restrictions resulting in plasma Phe concentrations of around 10 mg/dl. Preliminary results of the whole study are now presented.

Cognitive development of early treated PKU children (132) was investigated by intelligence tests, tests for visual perception, motor and language development. Deviations from test norms occurred at 5 years of age concerning performance IQ, mathematical thinking, and visual perception. With the exception of mathematical thinking, "normal" results were obtained at the age of 6 years. Correlation with levels of plasma Phe revealed a relation between quality of dietary control and performance IQ. Results are discussed in light of methodological aspects and with respect to treatment consequence.

The daily Phe intakes of normally growing 1- to 6-year-old treated PKU patients were evaluated. The children received protein in amounts that varied from 2.26 +/- 0.47 g/kg body weight per day (mean +/- SD) at the age of 6 to 1.81 +/- 0.35 at the age of 72 months. Mean Phe intakes declining from 34 +/- 7 at the age of 6 months to 15 +/- 5 mg/kg body weight per day at the age of 72 months were required to maintain mean median plasma Phe levels around 6.0 mg/dl.