Psychiatric disorders in adolescent and young adult patients with phenylketonuria

Background and objectives: Psychiatric symptoms are a challenging aspect in adolescent and adult early treated phenylketonuric (ETPKU) patients. To assess the occurrence of psychiatric disorders we explored the presence of symptoms requiring intervention and further investigated the link between psychiatric disorders, the quality of biochemical control and cognitive functioning. Patients and methods: Forty-six ETPKU patients (aged 12 to 44) and 30 age-matched healthy controls were sub- jected to cognitive and psychiatric assessment by means of self-report questionnaires and psychiatric interview. Psychiatric diagnoses, if detected, were made according to DSM-5 criteria. Concomitant IQ, historical and concur- rent biochemical metabolic controls were included in the statistical analysis. Results: Twenty-five out of 46 ETPKUs showed clinical scores on at least one scale of the psychiatric assessment (7/30 in controls); anxiety and withdrawal were the most frequent self-reported symptoms. Seventeen patients (and no controls) met criteria for a psychiatric diagnosis, most of them belonging to the Anxiety Disorders cate- gory. The occurrence of psychiatric symptoms was not associated with the life-long and concurrent quality of metabolic control but patients with good metabolic control (≤ 500 μM) in the first 11 years of life showed higher frequency of psychiatric diagnosis (Fisher's exact p = .0300). Discussion/conclusion: ETPKUs show a higher than normal vulnerability to psychiatric disorders, which cannot be explained by the usual biochemical alterations influencing intellectual outcome. Our data support the hypothesis that the burden of the disease acts as psychological stress for children and their families. Possible involvement of neuromediators in the pathogenesis of these complex symptoms requires further investigation.