J. Inher. Metab. Dis. 18 (1995) 131-134 © SSIEM and Kluwer Academic Publishers. Printed in the Netherlands Short Communication Improvements in behaviour and physical manifestations in previously untreated adults with phenylketonuria using a phenylalanine- restricted diet: a national survey S. YANNICELLIand A. RYAN Ross Products Division~Abbott Laboratories, 625 Cleveland Avenue, Columbus, OH, 43215-1724, USA Untreated adults with phenylketonuria (PKU; McKusick 261600) born prior to newborn screening may have abnormal electroencephalograms, seizures, neurological and behavioural disorders, a distinctive musty odour, eczema, and profound mental retardation. Behavioural aberrations in these individuals include hyperactivity, aggressiveness, negative mood swings, motor and attention disturbances, and self- inflicted injury (Brunner et al 1987; Scriver et al 1989). Behavioural improvement has been reported in previously untreated adults with PKU after introduction of a phenylalanine (PHE)-restricted diet with a subsequent reduction in plasma PHE concentrations (Hambraeus et al 1971; Harper and Reid 1987; Giffin et al 1980; Yannicelli et al 1990; Hoskin et al 1992). Physical manifestations associated with untreated PKU have been ameliorated with proper administration of a PHE-restricted diet and subsequent decline in plasma PHE concentration (Yannicelli et al 1990). Despite the documented positive behavioural response to a PHE-restricted diet in untreated adults, there have been some concerns. Gilpin et al (1993) reported increased frequency of aggressive behaviour and recurrence of seizure disorders in some individuals after diet initiation. Marholin et al (1978) also reported self-abusive behaviour in one patient given a PHE-restricted diet. Regardless of these few negative case reports, clinicians consider nutrition support a viable therapy for these patients. Most of the reports on the effectiveness of introducing a PHE-restricted diet have either been individual case studies or have been on small numbers of patients. We attempted to identify the effectiveness of diet intervention in previously untreated adults with a large national survey. METHODS A survey was developed to evaluate whether the introduction of a PHE-restricted diet with a concomitant reduction in plasma PHE concentration was associated with 131