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Regression of neuropsychological deficits in early-treated phenylketonurics during adolescence

  • Published:
Journal of Inherited Metabolic Disease

Abstract

Even early-treated phenylketonuric patients suffer from phenylalanine-associated (mild) neuropsychological impairment. To date it is still unclear whether patients' deficits show a progression on ageing. This unsolved question seems to be an important aspect in the still ongoing debate about how long and how strictly the patients should be maintained on diet. Twenty early-treated (20±10, 9–30 days) adolescent phenylketonurics (10 boys, 10 girls) and 20 healthy controls, matched for age, sex and IQ, were inves-tigated twice at a mean ages of 11 and 14 years for their IQ (Culture Fair Intelligence Test–Scale 2; CFT-20), fine motor abilities (Motor PerformanceTask), sustained (Test d2) and selective attention (Stroop-Task). At the first test, examinations revealed significant blood phenylalanine-correlated neuropsychological deficits in PKU patients. In spite of raised blood phenylalanine concentrations during the following 3 years and significantly elevated concurrent blood phenylalanine concentrations, the repeated measurements revealed a significant decrease of patients' deficits compared to controls. Clinical-neurological status of patients and controls was normal at both test times. The results indicate a decreased vulnerability of PKU-patients with respect to their neuropsychological functioning against elevated blood phenylalanine levels on ageing.

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References

  • APS (Stellungnahme der Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen) (1990) Diätetische Behandlung der Phenylketonurie. Monatsschr Kinderheilkd 138: 636.

    Google Scholar 

  • Bäumler G (1985) Farbe Wort Interferenz Test (FW IT ) nach JR Stroop. Göttingen: Verlag für Psychologie, 1-75.

    Google Scholar 

  • Bench CJ, Frith CJ, Gasby PM, Friston KJ, Frankowiak RSJ, Dolan RJ (1993) Investigations of the functional anatomy of attention using the Stroop test. Neuropsychology 31: 907-922.

    Google Scholar 

  • Bortz J (1983) Statistik. Berlin: Springer-Verlag.

    Google Scholar 

  • Brickenkamp R (1994) Test d 2 Aufmerksamkeits-Belastungs-Test. Göttingen: Verlag für Psychologie, 1-98.

    Google Scholar 

  • Brunner RL, Berry HK (1987) Phenylketonuria and sustained attention: the continuous performance test. Int J Clin Neuropsychol 9: 68-70.

    Google Scholar 

  • Burgard P, Schmidt E, Rupp A, Schneider W, Bremer HJ (1996) Intellectual development of the patients of the German Collaborative Study of patients treated for phenylketonuria. Eur J Pediatr 155 (supplement 1): 33-38.

    Google Scholar 

  • Burgard P, Rey F, Rupp A, Abadie V, Rey J (1997) Neuropsychological functions in early treated patients with phenylketonuria on and off diet. Results of a cross-national and crosssectional study. Pediatr Res 41: 368-374.

    Google Scholar 

  • Cleary MA, Walter JH, Wraith JE, et al (1994) Magnetic resonance imaging of the brain in phenylketonuria. Lancet 344: 87-90.

    Google Scholar 

  • Diamond A (1994) Phenylalanine levels of 6 to 10 mg/dl may not be as benign as once thought. Acta Paediatr (Suppl) 407: 89-91.

    Google Scholar 

  • Faust D, Libon D, Pueschel S (1986) Neuropsychological functioning in treated phenylketonuria. Int J Psychiatry Med 16: 169-177.

    Google Scholar 

  • German Paediatric Society (1990) Stellungnahme der Arbeitsgemeinschaft für Pädiatrische Stoffwechselstörungen APS zur diätetischen Behandlung der Phenylketonurie. Monatsschr Kinderheilkd 138: 636.

    Google Scholar 

  • Griffiths P, Campbell R, Robinson P (1998) Executive function in treated phenylketonuria as measured by the one-back and two-back versions of the continuous performance task. J Inher Metab Dis 21: 125-135.

    Google Scholar 

  • Holtzman NA, Kronmal RA, van Doorninck W, Azen C, Koch R (1986) Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria. N Engl J Med 314: 593-598.

    Google Scholar 

  • Hommes FA (1994) Loss of neurotransmitter receptors by hyperphenylalaninemia in the MPH-5 mouse brain. Acta Paediatr (Suppl) 407: 120-121.

    Google Scholar 

  • Huttenlocher PR (1975) Synaptic density in frontal lobe cortex: developmental stages and effects of aging. Brain Res 163: 195-205.

    Google Scholar 

  • Kirkcaldy B (1986) Differential psychomotor skills in a clinical group. Pers Indiv Diff 7: 853-859.

    Google Scholar 

  • Lou HC, Güttler F, Lykkelund C, Bruhn P, Niederwieser A (1985) Decreased vigilance and neurotransmitter synthesis after discontinuation of dietary treatment for phenylketonuria in adolescents. Eur J Pediatr 144: 17-20.

    Google Scholar 

  • Lou HC, Lykkelund C, Gerdes AM, Udesen H, Bruhn P (1987) Increased vigilance and dopamine synthesis by large doses of tyrosine or phenylalanine restriction in phenylketonuria. Acta Paediatr 76: 560-565.

    Google Scholar 

  • McKean CM (1972) The effects of high phenylalanine concentrations on serotonin and catecholamine metabolism in the human brain. Brain Res 47: 469-476.

    Google Scholar 

  • Medical Research Council Working Party on Phenylketonuria (1993) Recommendations on the dietary management of phenylketonuria. Arch Dis Child 68: 426-427.

    Google Scholar 

  • Milner JD, Wurtman RJ (1986) Effects of phenylalanine on the release of endogenous dopamine from rat striatal slices. J Neurochem 47: 1444-1448.

    Google Scholar 

  • Pardo JV, Pardo PJ, Janer KW, Raichle ME (1990) The anterior cingulate cortex mediates processing selection in the Stroop attentional conflict paradigm. Proc Natl Acad Sci USA 87: 256-259.

    Google Scholar 

  • Perret E (1974) The left frontal lobe of man and the suppression of habitual responses in verbal categorical behaviour. Neuropsychology 12: 323-330.

    Google Scholar 

  • Pietz J, Fätkenheuer B, Burgard P, Armbruster M, Esser G, Schmidt H (1997) Psychiatric disorders in adult patients with early treated phenylketonuria. J Pediatr 99: 345-350.

    Google Scholar 

  • Pratt OE (1992) Transport inhibition in the pathology of phenylketonuria and other inherited metabolic diseases. J Inher Metab Dis 2 (supplement 2): 75-81.

    Google Scholar 

  • Quatember R, Maly J (1980) Neuropsychologische Untersuchungsmethoden altersspezifischer Leistungsparameter. Wien Med Wochenschr 30: 688-692.

    Google Scholar 

  • Rey F, Abadie V, Plainguet F, Rey J (1996) Long-term follow up of patients with classical phenylketonuria after diet relaxation at 5 years of age. The Paris Study. Eur J Pediatr 155 (supplement 1): 39-44.

    Google Scholar 

  • Ris MD, Weber AM, Hunt MM, Berry HK, Williams SE, Leslie N (1997) Adult psychosocial outcome in early-treated phenylketonuria. J Inher Metab Dis 20: 499-508.

    Google Scholar 

  • Schmidt E, Rupp A, Burgard P, Pietz J, Weglage J, Sonneville de L (1994) Sustained attention in adult phenylketonuria: the influence of the concurrent phenylalanine blood level. J Clin Exp Neuropsychol 16: 681-688.

    Google Scholar 

  • Schmidt E, Burgard P, Rupp A (1996) Effects of concurrent phenylalanine levels on sustained attention and calculation speed in patients treated early for phenylketonuria. Eur J Pediatr 155 (supplement 1): 82-88.

    Google Scholar 

  • Schoppe KJ (1974) Das MLS-Gerät: Ein neuer Testapparat zur Messung feinmotorischer Leistungen. Diagnostica 20: 43-46.

    Google Scholar 

  • Scriver CR, Kaufman S, Eisensmith RC, Woo SLC (1995) The hyperphenylalaninemias. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Diseases, 7th edn. New York: MacGraw-Hill, 1015-1076.

    Google Scholar 

  • Smith I (1994) Treatment of phenylalanine hydroxylase defficiency. Acta Paediatr (Suppl) 407: 60-65.

    Google Scholar 

  • Smith I, Beaseley MG, Ades AE (1991) Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria. Arch Dis Child 65: 311-316.

    Google Scholar 

  • Waisbren SE, Brown MJ, Sonneville de LMJ, Levy HL (1994) Review of neuropsychological functioning in treated phenylketonuria: an information processing approach. Acta Paediatr (Suppl) 407: 98-103.

    Google Scholar 

  • Weglage J, Fünders B, Wilken B, et al (1992) Psychological and social findings in adolescents with phenylketonuria. Eur J Pediatr 151: 522-525.

    Google Scholar 

  • Weglage J, Fünders B, van Teefflen-Heithoff A, Ullrich K (1993) Behandlung der Phenylketonurie: Wunsch und Wirklichkeit. Monatsschr Kinderheilkd 141: 670-674.

    Google Scholar 

  • Weglage J, Pietsch M, Fünders B, Koch HG, Ullrich K (1995) Neurological findings in early treated phenylketonuria. Acta Paediatr 84: 411-415.

    Google Scholar 

  • Weglage J, Pietsch M, Fünders B, Koch HG, Ullrich K (1996) Deficits in selective and sustained attention processes in early treated children with phenylketonuria-result of impaired frontal lobe functions? Eur J Pediatr 155: 200-204.

    Google Scholar 

  • Weiss RH (1987) Grundintelligenztest Skala 2 CFT 20. Göttingen: Verlag für Psychologie, pp 1-67.

    Google Scholar 

  • Welsh MC, Pennington BF, Ozonoff S, Rouse B, McCabe ERB (1990) Neuropsychology of early treated phenylketonuria: specific executive function deficits. Child Dev 61: 1697-1713.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Münster, Münster, Germany

    J. Weglage, M. Pietsche, J. Denecke, A. Sprinz, R. Feldman & M. Grenzebach

  2. Department of Pediatrics, University of Hamburg, Hamburg, Germany

    K. Ullrich

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  1. J. Weglage
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  2. M. Pietsche
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  3. J. Denecke
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  4. A. Sprinz
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  5. R. Feldman
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  6. M. Grenzebach
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  7. K. Ullrich
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Weglage, J., Pietsche, M., Denecke, J. et al. Regression of neuropsychological deficits in early-treated phenylketonurics during adolescence. J Inherit Metab Dis 22, 693–705 (1999). https://doi.org/10.1023/A:1005587915468

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