Long-term development of intelligence (IQ) and EEG in 34 children with phenylketonuria treated early

Abstract

In 34 children with phenylketonuria (PKU) treated early the prognostic value of the age on institution of the diet (within the first 3 months of life) and of the quality of dietary treatment was determined in two different ways: 1) following intelligence closely (IQ) and (2) evaluating the EEG development up to their 12th (n = 34) and 15th (n = 18) years of life as appropriate. In general, IQ scores were found to be normal from the 4th-15th years of life. In our group of patients there was no effect on the IQ of the timing of diet onset. Children with "strict" dietary control showed a significantly higher IQ than those with "loose" control. One hundred and fifty-four EEGs (10/20 system, awake with eyes closed) were recorded at intervals of 2 years and conventionally evaluated. The development of alpha-activity was found to be normal. Beta-activity was enhanced. Abnormal EEG findings like general slowing and generalized paroxysmal activity (GPA) with or without spikes were more frequent in children with PKU than in controls, with the exception of focal abnormalities. EEG abnormalities increased with advancing age independently of IQ development and showed no relation to either the age at the onset nor the quality of dietary treatment.

Comparison of different indices of dietary control in phenylketonuria

“…A patient is under poor control if his phenylalanine levels are higher than the recommendation for the next age period. In summary, the IDCs reported above represent three different types of parameters: (I) Continuous variables (13,15,16,20); (11) frequency distributions of phenylalanine value intervals (18,19); (111) discrete or classifying systems of dietary control (12,16,17).…”

Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997

“…Abnormal EEG ®ndings such as general slowing and generalised paroxysmal activity with and without spikes increase with age but are not regarded as crucial for decisions about treatment [52]. Peaks of mean visually evoked potentials (VEP) were signi®cantly prolonged in about 30% of patients with PKU but were uncorrelated with age at start of treatment, and not associated with clinical abnormalities, MRI scans or any parameter of biochemical control [4, 5, 38,55].…”

Pregnancy in phenylketonuria: dietary treatment aimed at normalising maternal plasma phenylalanine concentration.

“…The potentially disastrous effects of phenylalanine deprivation,'3 the poor reliability of filter paper blood spot assay of low phenylalanine concentration,8 and the apparently good outcome of PKU treated by maintaining plasma phenylalanine concentration a little above normal,'4 15 have led to the great reluctance to maintain phenylalanine concentrations in children with PKU within the normal range.…”