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- W84246427 abstract "PKU is a genetically inherited inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase. The failure of this enzyme causes incomplete metabolism of protein ingested in the diet, specifically the conversion of one amino acid, phenylalanine, to tyrosine, which is a precursor to the neurotransmitter dopamine. Rising levels of phenylalanine is toxic to the developing brain, disrupting the formation of white matter tracts. The impact of tyrosine deficiency is not as well understood, but is hypothesized to lead to a low dopamine environment for the developing brain. Detection in the newborn period and continuous treatment (a low protein phe-restricted diet supplemented with phenylalanine-free protein formulas) has resulted in children with early and continuously treated PKU now developing normal I.Q. However, deficits in executive function (EF) are common, leading to a rate of Attention Deficit Hyperactivity Disorder (ADHD) up to five times the norm. EF worsens with exposure to higher phenylalanine levels, however recent research has demonstrated that a high phenylalanine to tyrosine ratio (phenylalanine:tyrosine ratio), which is hypothesised to lead to poorer dopamine function, has a more negative impact on EF than phenylalanine levels alone. Research and treatment of PKU is currently phenylalanine-focused, with little investigation of the impact of tyrosine on neuropsychological development. There is no current consensus as to the veracity of tyrosine monitoring or treatment in this population. Further, the research agenda in this population has demonstrated a primary focus on EF impairment alone, even though there may be additional neuropsychological skills compromised (e.g., mood, visuospatial deficits). The aim of this PhD research was to identify residual neuropsychological deficits in a cohort of children with early and continuously treated phenylketonuria, at two time points in development (early childhood and early adolescence), separated by eight years. In addition, this research sought to determine which biochemical markers were associated with neuropsychological impairments. A clinical practice survey was also undertaken to ascertain the current level of monitoring/treatment of tyrosine in this population.Thirteen children with early and continuously treated PKU were tested at mean age 5.9 years and again at mean age 13.95 years on several neuropsychological measures. Four children with hyperphenylalaninemia (a milder version of PKU) were also tested at both time points and provide a comparison group in analyses. Associations between neuropsychological function and biochemical markers were analysed. A between groups analysis in adolescence was also conducted (children with PKU compared to their siblings) on parent report measures of EF and mood. Minor EF impairments were evident in the PKU group by age 6 years and these persisted into adolescence. Life-long exposure to high phenylalanine:tyrosine ratio and/or low tyrosine independent of phenylalanine were significantly associated with EF impairments at both time points. Over half the children with PKU showed severe impairment on a visuospatial task, and this was associated only with concurrent levels of tyrosine in adolescence. Children with PKU also showed a statistically significant decline in a language comprehension task from 6 years to adolescence (going from normal to subnormal), this deficit was associated with lifetime levels of phenylalanine. In comparison, the four children with hyperphenylalaninemia demonstrated normal function at both time points, across all measures. No statistically significant differences were detected between children with PKU and their siblings on the parent report of EF and mood. However, depressive symptoms were significantly correlated with: EF; long term high phe:tyr exposure; and low tyrosine levels independent of phenylalanine. The practice survey of metabolic clinics from 12 countries indicated a high level of variability in terms of monitoring/treatment of tyrosine in this population. Whilst over 80% of clinics surveyed routinely monitored tyrosine levels in their child patients, 25% reported treatment strategies to increase tyrosine (and thereby lower the phenylalanine:tyrosine ratio) under a variety of patient presentation conditions. Overall, these studies have shown that EF impairments associated with PKU provide support for the dopamine-deficiency model. A language comprehension task showed a different trajectory, serving a timely reminder that non-EF functions also remain vulnerable in this population; and that normal function in childhood does not guarantee normal function by adolescence. Mood impairments were associated with EF impairments as well as long term measures of phenylalanine:tyrosine and/or tyrosine. The implications of this research for enhanced clinical guidelines are discussed given varied current practice." @default.
- W84246427 created "2016-06-24" @default.
- W84246427 creator A5065552217 @default.
- W84246427 date "2011-01-01" @default.
- W84246427 modified "2023-09-24" @default.
- W84246427 title "Neuropsychological development in children with early and continuously treated phenylketonuria : association with biochemical markers" @default.
- W84246427 cites W1489923144 @default.
- W84246427 cites W1537784663 @default.
- W84246427 cites W1538259514 @default.
- W84246427 cites W1685870920 @default.
- W84246427 cites W1937541206 @default.
- W84246427 cites W1966577228 @default.
- W84246427 cites W1971772651 @default.
- W84246427 cites W1973371295 @default.
- W84246427 cites W1977842550 @default.
- W84246427 cites W1981412704 @default.
- W84246427 cites W1982975044 @default.
- W84246427 cites W1984655161 @default.
- W84246427 cites W1989323794 @default.
- W84246427 cites W1991040972 @default.
- W84246427 cites W1992214296 @default.
- W84246427 cites W1995375488 @default.
- W84246427 cites W1997901745 @default.
- W84246427 cites W2004795925 @default.
- W84246427 cites W2008123860 @default.
- W84246427 cites W2008457092 @default.
- W84246427 cites W2013134165 @default.
- W84246427 cites W2013520266 @default.
- W84246427 cites W2015236580 @default.
- W84246427 cites W2015421768 @default.
- W84246427 cites W2021999429 @default.
- W84246427 cites W2023758221 @default.
- W84246427 cites W2026606034 @default.
- W84246427 cites W2030835068 @default.
- W84246427 cites W2035599443 @default.
- W84246427 cites W2048200506 @default.
- W84246427 cites W2049767453 @default.
- W84246427 cites W2057934986 @default.
- W84246427 cites W2059269927 @default.
- W84246427 cites W2060418959 @default.
- W84246427 cites W2061358063 @default.
- W84246427 cites W2064314001 @default.
- W84246427 cites W2066785847 @default.
- W84246427 cites W2068034170 @default.
- W84246427 cites W2069270123 @default.
- W84246427 cites W2069361380 @default.
- W84246427 cites W2072184486 @default.
- W84246427 cites W2074868905 @default.
- W84246427 cites W2075349529 @default.
- W84246427 cites W2078683397 @default.
- W84246427 cites W2081029456 @default.
- W84246427 cites W2086104219 @default.
- W84246427 cites W2089571812 @default.
- W84246427 cites W2091251508 @default.
- W84246427 cites W2092022059 @default.
- W84246427 cites W2094327570 @default.
- W84246427 cites W2094929193 @default.
- W84246427 cites W2099577231 @default.
- W84246427 cites W2101011631 @default.
- W84246427 cites W2102985587 @default.
- W84246427 cites W2103640205 @default.
- W84246427 cites W2111672643 @default.
- W84246427 cites W211409166 @default.
- W84246427 cites W2114313193 @default.
- W84246427 cites W2116248687 @default.
- W84246427 cites W2116316183 @default.
- W84246427 cites W2116366617 @default.
- W84246427 cites W2119242730 @default.
- W84246427 cites W2119637378 @default.
- W84246427 cites W2121154230 @default.
- W84246427 cites W2124517301 @default.
- W84246427 cites W2125210345 @default.
- W84246427 cites W2130008501 @default.
- W84246427 cites W2132374409 @default.
- W84246427 cites W2132423376 @default.
- W84246427 cites W2132820737 @default.
- W84246427 cites W2133016564 @default.
- W84246427 cites W2135187258 @default.
- W84246427 cites W2138340059 @default.
- W84246427 cites W2141200554 @default.
- W84246427 cites W2152508397 @default.
- W84246427 cites W2155215186 @default.
- W84246427 cites W2159974920 @default.
- W84246427 cites W2160613309 @default.
- W84246427 cites W2162050340 @default.
- W84246427 cites W2167207812 @default.
- W84246427 cites W2170784653 @default.
- W84246427 cites W2361556524 @default.
- W84246427 cites W2592976990 @default.
- W84246427 cites W2799137111 @default.
- W84246427 cites W2885150882 @default.
- W84246427 cites W2992873079 @default.
- W84246427 cites W31760838 @default.
- W84246427 cites W45871736 @default.
- W84246427 cites W177478576 @default.
- W84246427 cites W2114529541 @default.
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