Behaviour in early treated phenylketonuria: a systematic review

A search was made of the literature on behaviour in early treated phenylketonuria (PKU). Some 34 publications were selected for systematic review in order to answer the following questions: (1) does behaviour in early treated subjects with PKU differ from that in the general population?, (2) if so, do the differences show any consistent pattern?, matter in real life?, relate to intellectual status, phenylalanine (Phe) control or social factors? and (3) can behavioural problems be precipitated or reversed by changes in Phe control?. Eleven reports based on four studies of >20 subjects provided the most useful data. There was good evidence of differences between subjects with PKU and their unaffected peers in behaviour and perception of self. The pattern of results was consistent across nations and age groups (higher scores on emotional/neurotic items and lower scores on anti-social/aggressive items) and suggested that subjects with PKU are more prone to depression, anxiety, phobic tendencies, isolation from their peers and a less “masculine” self image. Features of attention deficit hyperactivity disorder and associations between behaviour problems and both lower IQ and a worse quality of Phe control were well documented in several studies.