A comparison of phenylketonuria with attention deficit hyperactivity disorder: Do markedly different aetiologies deliver common phenotypes?

作者：Stevenson M; McNaughton N^*

来源：Brain Research Bulletin, 2013, 99: 63-83.

DOI：10.1016/j.brainresbull.2013.10.003

• Attention deficit hyperactivity disorder
• Behavioural Inhibition System
• Dopamine
• Phenylketonuria
• Prefrontal cortex
• White matter

Phenylketonuria (PKU) is a well-defined metabolic disorder arising from a mutation that disrupts phenylalanine metabolism and so produces a variety of neural changes indirectly. Severe cognitive impairment can be prevented by dietary treatment; however, residual symptoms may be reported. These residual symptoms appear to overlap a more prevalent childhood disorder: Attention Deficit/Hyperactivity Disorder (ADHD). However, the aetiology of ADHD is a vast contrast to PKU: it seems to arise from a complex combination of genes; and it has a substantial environmental component. We ask whether these two disorders result from two vastly different genotypes that converge on a specific core phenotype that includes similar dysfunctions of Gray%26apos;s (Gray, 1982) Behavioural Inhibition System (BIS), coupled with other disorder-specific dysfunctions. If so, we believe comparison of the commonalities will allow greater understanding of the neuropsychology of both disorders. We review in detail the aetiology, treatment, neural pathology, cognitive deficits and electrophysiological abnormalities of PKU; and compare this with selected directly matching aspects of ADHD. The biochemical and neural pathologies of PKU and ADHD are quite distinct in their causes and detail; but they result in the disorder in the brain of large amino acid levels, dopamine and white matter that are very similar and could explain the overlap of symptoms within and between the PKU and ADHD spectra. The common deficits affect visual function, motor function, attention, working memory, planning, and inhibition. For each of PKU and ADHD separately, a subset of deficits has been attributed to a primary dysfunction of behavioural inhibition. In the case of ADHD (excluding the inattentive subtype) this has been proposed to involve a specific failure of the BIS; and we suggest that this is also true of PKU. This accounts for a substantial proportion of the parallels in the superficial symptoms of both disorders and we see this as linked to prefrontal, rather than more general, dysfunction of the BIS.

• 出版日期2013-10