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Neuropsychological functioning in children with early-treated phenylketonuria: impact of white matter abnormalities
Peter J Anderson1, Stephen J Wood, Dorothy E Francis
1Department of Psychology, Royal Children's Hospital, Melbourne, Victoria, Australia. anderson@cryptic.rch.unimelb.edu.au
Insights
White matter abnormalities (WMAs) significantly impact cognitive function in children with early-treated phenylketonuria (ETPKU), especially when WMAs affect frontal regions. Neuropsychological deficits in ETPKU are complex, influenced by both brain structure and metabolic factors.
Area of Science:
- Neuroscience
- Pediatrics
- Metabolic Disorders
Background:
- Phenylketonuria (PKU) is a genetic disorder requiring early treatment to prevent severe intellectual disability.
- White matter abnormalities (WMAs) are common in treated PKU, but their specific impact on cognitive function requires further elucidation.
- Understanding the relationship between WMAs and neuropsychological outcomes is crucial for optimizing management strategies in early-treated PKU (ETPKU).
Purpose of the Study:
- To investigate the impact of white matter abnormalities (WMAs) on neuropsychological functioning in children with early-treated phenylketonuria (ETPKU).
- To determine the relationship between the extent and location of WMAs and specific cognitive deficits.
- To explore the influence of phenylalanine levels on cognitive outcomes in ETPKU.
Main Methods:
- Neuropsychological assessments were conducted on children with ETPKU and age-matched controls, evaluating attention, processing speed, memory, executive function, and academic achievement.
- Magnetic resonance imaging (MRI) was used to identify and characterize WMAs in participants.
- Statistical analyses examined correlations between WMA severity/location and cognitive performance, as well as associations with phenylalanine levels.
Main Results:
- Children with ETPKU and WMAs extending into subcortical/frontal regions showed significant cognitive impairments.
- ETPKU patients with no WMAs or only posterior periventricular WMAs exhibited milder deficits.
- Lifetime phenylalanine levels, but not concurrent levels, correlated with deficits in several cognitive domains.
Conclusions:
- Extensive WMAs in ETPKU are associated with compromised neural transmission and dysmyelination, leading to significant cognitive impairments.
- Even in the absence of significant WMAs, children with ETPKU can experience cognitive problems, suggesting a multifactorial etiology.
- Neuropsychological functioning in ETPKU is influenced by a complex interplay of biological factors (WMAs, phenylalanine levels) and environmental influences.
Abstract:
Impact of white matter abnormalities (WMAs) on neuropsychological functioning in children with early-treated phenylketonuria (ETPKU) was examined. Children with ETPKU (20 males, 12 females, mean age 11 years 2 months, SD 3 years 6 months) and controls (20 males, 14 females, mean age 10 years 4 months, SD 3 years 1 month) aged 7 to 18 years were assessed using tests of attention, processing speed, memory and learning, executive function, and academic achievement. Those with ETPKU, exhibiting WMAs extending into subcortical/frontal regions (n=14), displayed significant impairments in a number of domains. Children with ETPKU but no WMAs (n=6), or pathology restricted to the posterior periventricular region (n=12), displayed only mild deficits. Concurrent phenylalanine levels correlated weakly with cognitive parameters, whereas lifetime phenylalanine levels were associated with deficits in several cognitive domains. Impairments in children with extensive WMAs are consistent with compromised neural transmission, which is characterized by dysmyelination. However, children with no detectable, or mild WMAs, also displayed cognitive problems, indicating that neuropsychological functioning in children with ETPKU is determined by a complex interaction of biological and environmental factors.
