[The IQ of heterozygotes for phenylketonuria (PKU). indication of a blood phenylalanine-independent action of the PKU mutant (author's transl)].

The IQ of parents of phenylketonuria-(PKU-)affected children is lower than that of parents with histidinemia-affected children (control group). The difference arises almost entirely from the verbal part of the Hamburg-Wechsler test. The IQ of the parents with histidinemia-affected children shows the same distribution as that of the normal population; heterozygosity for this condition does not appear to confer any intellectual advantage. In PKU patients treated at an early age and apparently adequately, a slight, but significant decrease in IQ becomes apparent between the ages of 6 and 8 years. This slight decrease also refers mainly to the verbal IQ. At 4 years of age all PKU patients are tested with Bühler-Hetzer, as well as the Kramer test. There is a significant difference between the results in favour of the Bühler-Hetzer test, which is much less verbal. Since heterozygotes for PKU never show elevated blood phenylalanine levels and, moreover, prenatal tyrosine deficiency, as argued by others, seems highly improbable, it is supposed that the PKU gene has a more direct influence on certain ganglion cells at least, with a consequent slight, but significant lowering of the verbal IQ in heterozygotes and satisfactorily-treated homozygotes for PKU. A slightly increased intracellular phenylalanine concentration in heterozygotes and apparently adequately-treated homozygotes need not to be reflected in raised blood levels and this could be an explanation for the observed IQ lowering. But it should not be overlooked that by far the greatest part of damage in PKU patients is caused by chronic phenylalanine poisoning which is well preventable by correct dietary treatment.