Executive function impairment in early-treated PKU subjects with normal mental development

Area of Science:

• Neuroscience
• Pediatrics
• Metabolic Disorders

Background:

• Phenylketonuria (PKU) is a genetic disorder requiring early and continuous dietary management.
• Executive functions are complex cognitive processes crucial for daily life.
• The impact of long-term phenylalanine (Phe) exposure on executive functions in treated PKU patients requires further investigation.

Purpose of the Study:

• To assess executive functions in early and continuously treated PKU patients compared to controls.
• To investigate the relationship between dietary control quality and executive function performance in PKU.
• To determine the optimal blood Phe concentration target for preventing frontal lobe dysfunction.

Main Methods:

• Neuropsychological evaluation of 14 early-treated PKU subjects (ages 8-13) using various executive function tests.
• Comparison with age, sex, IQ, and socioeconomic status-matched controls.
• Subgroup analysis based on dietary control quality (blood Phe < or > 400 micromol/L).

Main Results:

• PKU subjects performed significantly worse than controls on executive function tests, irrespective of IQ.
• Poorer dietary control (higher Phe levels) correlated with more significant executive function deficits.
• Mild executive function impairments were observed even in PKU patients with good dietary control (Phe <400 micromol/L).

Conclusions:

• Early and continuous PKU treatment does not fully prevent frontal lobe function impairment.
• Prolonged exposure to elevated Phe levels can negatively impact executive functions independently of IQ.
• Maintaining blood Phe below 400 micromol/L is recommended to mitigate the risk of frontal lobe dysfunction in PKU.