Neuropsychological profile of French adults with early-treated phenylketonuria: a multicenter study

Adult patients with early-treated phenylketonuria (AwET-PKU) may present some subtle neurocognitive deficits. The aim of the study was to investigate 1) neurocognitive functions in a large group of AwET-PKU 2) the influence of plasma phenylalanine (Phe).

Participants: 187 AwET-PKU (classic PKU [cPKU] 81%, mild PKU [mPKU] 14%, and mild persistent hyperphenylalaninemia [MPH] 5%). Cognitive assessments: tests included the Wechsler Adult Intelligence Scale-IV, California Verbal Learning Test-II, Trail Making Test, and verbal fluency tests. Biochemical data: plasma Phe was measured concurrently with cognitive assessments.

Episodic memory: cPKU patients had lower performance in immediate recall compared to mPKU patients. There was a negative correlation between Phe levels and immediate recall indices, but no correlation with delayed memory. Processing speed: cPKU patients performed worse than mPKU patients in processing speed tests. Negative correlations were observed between Phe levels and processing speed measures, with more pronounced effects in cPKU patients. Executive functioning: No differences were found between cPKU and mPKU patients on executive functioning tests. No correlation was found between executive function and Phe levels. Working memory: cPKU patients had poorer working memory performance compared to mPKU patients, though no correlation was found between working memory performance and Phe levels.

The study reveals neurocognitive deficits in adults with PKU, particularly in episodic memory and processing speed. Higher plasma Phe levels are associated with poorer performance in these areas, especially in cPKU patients. Working memory and executive functioning did not show significant correlations with Phe levels.