Cognitive Functioning in Adults with Phenylketonuria in a Cohort of Spanish Patients

Abstract

The early introduction of a low phenylalanine (Phe) diet has been demonstrated to be the most successful treatment in subjects with phenylketonuria (PKU), especially for preventing severe cognitive and neurological damages. However, it still concerns that even if treated in the first months of life with supplements and following a diet, they can show slight scores below people without PKU in neuropsychological assignments. We investigated 20 adults with classical PKU aged 19–48 years (mean age 29 years) and 20 heathy controls matched by age, gender, and years of education. Patients and controls were assessed with an extended neuropsychological battery, as well as psychological aspects and quality of life, also the last Phe level result was obtained. Results showed that the most affected cognitive domains are processing speed, executive functioning, memory, and also theory of mind, but very well-preserved verbal fluency, language, and visuospatial functioning. In quality of life, some significant results were seen specially in anxiety of Phe levels, anxiety of Phe levels during pregnancy, guilt if poor adherence to supplements, and if dietary protein restriction not followed. No significant results were obtained for the psychological variables. In conclusion, it has been shown that a combination of a low Phe diet, supplement intake, and keeping Phe levels in a low range seems appropriate to have the most normal and alike cognitive performance to persons without PKU.

Cerebral blood flow and white matter alterations in adults with phenylketonuria

“…Regarding cognitive functioning, patients’ IQ was within the normal range but significantly lower than the control group such as presented in previous studies ( Feldmann et al, 2019 , Jahja et al, 2017 , Palermo et al, 2017 ). Also, processing speed, working memory performance, cognitive flexibility, and sustained attention were significantly reduced in patients compared to healthy controls, which is in accordance with previous studies ( Ashe et al, 2019 , Christ et al, 2010 , Hofman et al, 2018 , Luna et al, 2023 ). None of the cognitive domains were associated with metabolic parameters, global or regional CBF, or with white matter lesions.…”

“…The impaired conversion of the amino acid phenylalanine (Phe) into tyrosine leads to high Phe levels and low-to-normal plasma tyrosine concentrations. If infants and children with PKU are left untreated, severe and irreversible neurological and cognitive sequelae occur, such as mental disabilities, behavioral and psychiatric problems, tremor, or epilepsy ( Blau et al, 2010 , Luna et al, 2023 ). An early-initiated dietary protein restriction combined with Phe-free amino acid supplementation prevents the development of severe clinical symptoms ( van Spronsen et al, 2021 ).…”