Inhibitory Control in Children With Phenylketonuria

Department of Psychological Sciences, University of Missouri-Columbia, Department of Psychology, Washington University, St. Louis, MO 65211, USA.
Developmental Neuropsychology (Impact Factor: 2.24). 02/2006; 30(3):845-64. DOI: 10.1207/s15326942dn3003_5
Source: PubMed


Past studies have reported impairments in children with early-treated phenylketonuria (PKU) in executive abilities such as strategic processing and working memory. Findings have been inconsistent in terms of the integrity of inhibitory control, another executive ability. This study administered 4 inhibitory tasks (flanker, Stroop, go/no-go, antisaccade) to 26 children with PKU and 25 typically developing control children. Children with PKU performed more poorly than typically developing children on the 2 inhibitory tasks with the strongest experimental manipulations (go/no-go and antisaccade) between control and inhibitory conditions. Findings suggest that the inhibitory deficit associated with PKU is subtle and that inconsistent findings in past studies may be largely due to the insensitivity of experimental manipulations in some tasks.

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    • "In particular, patients transitioning into adolescence and adulthood will demonstrate decreased dietary compliance and plasma Phe concentrations increased beyond the therapeutic range [3,4]. Although the consequences are not as severe as during infancy and young childhood, this noncompliance has been shown to lead to neurological sequelae such as increased risk of mood disorders [5], attention deficits [6,7], impairments to executive functioning [8-10], school performance and achievement [11], and social difficulties [12], issues which can certainly impact QOL. Past studies have implicated both high plasma Phe concentrations as well as the strict medical diet in reduced quality of life (QOL) for patients with PKU [13,14]. "
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    ABSTRACT: Sapropterin dihydrochloride effectively lowers plasma phenylalanine (Phe) for at least a third of phenylketonuria (PKU) patients, with potential for increased dietary Phe tolerance and decreased medical food requirement. To investigate long-term quality of life (QOL) in patients with phenylketonuria (PKU) who took sapropterin (BH4, Kuvan(R)) for up to one year. 37 PKU patients, ages 10-49 years, were asked to complete a PKU-specific self-report QOL questionnaire (QOLQ) at baseline, 1, 4, 8, and 12 months. Questions were scored on a 5-point Likert scale under 5 sub-sections measuring Impact, Worries, Satisfaction, Support, and General wellbeing in relation to PKU. Responders with a plasma Phe decrease >= 15% after 1 month on sapropterin remained on the drug; Nonresponders ceased sapropterin after the trial month. Responders able to relax medical diet and maintain plasma Phe control were classified as Definitive; Responders unable to relax medical diet were classified as Provisional. All patients were routinely monitored by a registered dietitian. Data was analyzed in SPSS 19.0 using regression techniques. Of 17 Responders, 11 could maintain adequate Phe control on a less restrictive diet. One year mean Impact sub-score trends improved significantly for all sapropterin response groups, with greatest improvement among Definitive Responders (p < 0.0001). Satisfaction sub-scores also improved for Definitive Responders (p = 0.001). Trends for Total QOL score improved significantly over time for both Definitive (p = 0.001) and Provisional Responders (p = 0.028). Improvements in Definitive Responder scores were associated with increased Phe tolerance (Impact: p < 0.0001, Satisfaction: p = 0.022, Total QOL: p = 0.005) and MF adjustment (Satisfaction: p = 0.014, Total QOL: p = 0.026). Other sub-section scores remained steady, unaffected by sapropterin response or diet modification. Increased Phe tolerance and reduced MF requirement in sapropterin Definitive Responders improves QOL perception across one year, specifically for life impact and satisfaction.
    Health and Quality of Life Outcomes 12/2013; 11(1):218. DOI:10.1186/1477-7525-11-218 · 2.12 Impact Factor
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    • "A variety of other factors have also been identified as affecting adult patients' ability to access appropriate treatment for PKU (Figure 1).27,28,29,30,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98 Psychiatric and executive function impairments such as attention and processing-speed deficits,73,77,80 behavioral and emotional problems,81 psychiatric disorders,73,81 and cognitive deficits73,81,82,83 may have an overall negative effect on the individual's quality of life. If an adult is not followed by a metabolic clinic, he or she may not know that diet treatment is now recommended for life or that new treatment options are available that may make adherence more attainable. "
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    ABSTRACT: Fifty years after the implementation of universal newborn screening programs for phenylketonuria, the first disease identified through newborn screening and considered a success story of newborn screening, a cohort of adults with phenylketonuria treated from birth provides valuable information about effects of long-term treatment for inborn errors of metabolism in general, and phenylketonuria specifically. For phenylketonuria, newborn screening allows early implementation of the phenylalanine-restricted diet, eliminating the severe neurocognitive and neuromotor impairment associated with untreated phenylketonuria. However, executive function impairments and psychiatric problems are frequently reported even for those treated early and continuously with the phenylalanine-restricted diet alone. Moreover, a large percentage of adults with phenylketonuria are reported as lost to follow-up by metabolic clinics. While a group of experts identified by the National Institutes of Health convenes to update treatment guidelines for phenylketonuria, we explore individual patient, social, and economic factors preventing >70% of adult phenylketonuria patients in the United States from accessing treatment. As more conditions are identified through newborn screening, factors affecting access to treatment grow in importance, and we must continue to be vigilant in assessing and addressing factors that affect patient treatment outcomes and not just celebrate amelioration of the most severe manifestations of disease.Genet Med advance online publication 7 March 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.10.
    Genetics in medicine: official journal of the American College of Medical Genetics 03/2013; 15(8). DOI:10.1038/gim.2013.10 · 7.33 Impact Factor
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    • "Further research will be required to resolve this discrepancy. With regard to resistance to distractor interference, the performance of individuals with early-treated PKU appears to be intact [16] [40] [44] [71]. Finally, evidence from one study [13] suggests that the third subtype of inhibitory control, resistance to proactive interference, may also be intact. "
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    ABSTRACT: Despite early and continuous dietary intervention, individuals with early-treated phenylketonuria (PKU) experience significant neurocognitive sequelae. An area of cognitive ability that is believed to be particularly affected is executive function (EF). This paper provides a critical review of the evidence for EF impairment in early-treated PKU within the context of recent advances in neuropsychological theory and research. The most consistent findings of PKU-related EF impairment were in executive working memory and prepotent response inhibition. Surprisingly, findings on shifting ability and other more complex aspects of EF were largely equivocal. Cohort (e.g., age, phenylalanine (Phe) levels) and task (e.g., standard clinical versus experimental tasks) related differences likely contributed to the variability in findings reported by these studies. Day-to-day EF also appears to be impaired although the precise pattern of impairment remains unclear, as does the relationship between laboratory measures of EF and questionnaires assessing day-to-day EF. Similarly, whereas several studies have found a relationship between Phe levels and EF, the best predictor variable (e.g., concurrent Phe level, lifetime Phe level, Phe level variability) of current EF performance varied from study to study. Neurologic compromise related to dopamine deficiency, white matter abnormalities, and disruptions in functional connectivity likely underlies the EF impairments described in this review. In closing, this review identifies remaining unanswered questions and future avenues for research.
    Molecular Genetics and Metabolism 12/2010; 99 Suppl 1:S22-32. DOI:10.1016/j.ymgme.2009.10.007 · 2.63 Impact Factor
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