Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?

Peter J. Anderson; Stephen J. Wood; Dorothy E. Francis; Lee Coleman; Vicki Anderson; Avihu Boneh

Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?

Peter J. Anderson, Stephen J. Wood, Dorothy E. Francis, Lee Coleman, Vicki Anderson, Avihu Boneh

Research output: Contribution to journal › Article › Research › peer-review

Abstract

This study aimed to enhance our understanding of neuropsychological functioning in children with early-treated phenylketonuria (PKU) and assess the relative impact of white matter abnormalities (WMA) and neurotransmitter deficiencies on cognitive functions in this population. The study consisted of 33 children with early-treated PKU and 34 healthy control children aged between 7 to 18 years. All children had a neuropsychological evaluation that included measures of general intelligence, attention, processing speed, memory and learning, executive function, and academic achievement. Children in the PKU group also had a magnetic resonance (MR) brain scan. When compared with the control group, the PKU group exhibited global cognitive impairment including lower IQ, attention problems, slow information processing, reduced learning capacity, mild executive impairments, and educational difficulties. Children in the PKU group with extensive WMA (n = 14) displayed significant impairments across all cognitive domains. Metabolic control correlated weakly to moderately with attention, executive, and memory/learning factors. Within the PKU group, regressions revealed that executive function and attention factors were independently related to severity of WM pathology and age, while the memory and learn-ing factor was independently related to metabolic control and age. It is concluded that children with early-treated PKU exhibit a global pattern of impairment, with a particular deficit in processing speed. WM pathology extending into frontal and subcortical regions correlates with the greatest deficits and a profile of impairment consistent with diffuse WM damage. Our findings also offer some support for dopamine depletion in the prefrontal cortex, however adverse consequences as a result of norepinephrine and serotonin deficiencies should not be discounted.

Original language	English
Pages (from-to)	645-668
Number of pages	24
Journal	Developmental Neuropsychology
Volume	32
Issue number	2
Publication status	Published - 2007
Externally published	Yes

Cite this

Anderson, P. J., Wood, S. J., Francis, D. E., Coleman, L., Anderson, V., & Boneh, A. (2007). Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels? Developmental Neuropsychology, 32(2), 645-668.

Anderson, Peter J. ; Wood, Stephen J. ; Francis, Dorothy E. ; Coleman, Lee ; Anderson, Vicki ; Boneh, Avihu. / Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?. In: Developmental Neuropsychology. 2007 ; Vol. 32, No. 2. pp. 645-668.

@article{68b19eadf90f493caa80fa32e290c27f,

title = "Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?",

abstract = "This study aimed to enhance our understanding of neuropsychological functioning in children with early-treated phenylketonuria (PKU) and assess the relative impact of white matter abnormalities (WMA) and neurotransmitter deficiencies on cognitive functions in this population. The study consisted of 33 children with early-treated PKU and 34 healthy control children aged between 7 to 18 years. All children had a neuropsychological evaluation that included measures of general intelligence, attention, processing speed, memory and learning, executive function, and academic achievement. Children in the PKU group also had a magnetic resonance (MR) brain scan. When compared with the control group, the PKU group exhibited global cognitive impairment including lower IQ, attention problems, slow information processing, reduced learning capacity, mild executive impairments, and educational difficulties. Children in the PKU group with extensive WMA (n = 14) displayed significant impairments across all cognitive domains. Metabolic control correlated weakly to moderately with attention, executive, and memory/learning factors. Within the PKU group, regressions revealed that executive function and attention factors were independently related to severity of WM pathology and age, while the memory and learn-ing factor was independently related to metabolic control and age. It is concluded that children with early-treated PKU exhibit a global pattern of impairment, with a particular deficit in processing speed. WM pathology extending into frontal and subcortical regions correlates with the greatest deficits and a profile of impairment consistent with diffuse WM damage. Our findings also offer some support for dopamine depletion in the prefrontal cortex, however adverse consequences as a result of norepinephrine and serotonin deficiencies should not be discounted.",

author = "Anderson, {Peter J.} and Wood, {Stephen J.} and Francis, {Dorothy E.} and Lee Coleman and Vicki Anderson and Avihu Boneh",

year = "2007",

language = "English",

volume = "32",

pages = "645--668",

journal = "Developmental Neuropsychology",

issn = "8756-5641",

publisher = "Taylor & Francis",

number = "2",

}

Anderson, PJ, Wood, SJ, Francis, DE, Coleman, L, Anderson, V & Boneh, A 2007, 'Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?' Developmental Neuropsychology, vol. 32, no. 2, pp. 645-668.