Skip to main content
SpringerLink
Log in

Executive Function in School-Aged Children with Phenylketonuria

  • Published:
Journal of Developmental and Physical Disabilities Aims and scope Submit manuscript

Abstract

The hypothesis that, by school age, children with early-treated phenylketonuria (PKU) have specific cognitive deficits in executive function skills was examined in 19 children with PKU and 19 age-, sex-, and IQ-matched control participants. Five tasks were used, three chosen to measure executive, or frontal-lobe, functions (problem-solving, working memory, and verbal fluency) and two as control measures (verbal memory and spatial perception). Children with PKU performed more poorly on the problem-solving task and on the verbal memory task, suggesting that cognitive impairments associated with PKU persist into the school-age years. In addition, cognitive performance among the children with PKU was found to be specific to the phenylalanine (phe) levels at the time of testing. The high-phe group performed consistently more poorly than the control group on four of the six measures of the problem-solving task and on the verbal memory task, whereas the low-phe group was comparable to the control group on all measures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Becker, M. G., Isaac, W., and Hynd, G. W. (1987). Neuropsychological development of nonverbal behaviours attributed to frontal lobe functioning. Dev. Neuropsychol3: 275-298.

    Google Scholar 

  • Benton, A. L. (1969). Disorders of spatial orientation. In Vinken, P. J., and Bruyn, G. W. (eds.), Handbook of Clinical Neurology, Vol. 3. Disorders of Higher Nervous Activity, Wiley, New York.

    Google Scholar 

  • Berry, H. K., Bofinger, M. K., O'Grady, D. J., and Perlmutter, L. J. (1979). Intellectual development and academic achievement of children treated early for phenylketonuria. Dev. Med. Child Neurol.21: 311-320.

    Google Scholar 

  • Brodal, A. (1981). Neurological Anatomy, Oxford University Press, New York.

    Google Scholar 

  • Brunner, R. L., Jordan, M. K., and Berry, H. K. (1983). Early-treated phenylketonuria: Neuropsychologic consequences. J. Pediatr.102(6): 831-835.

    Google Scholar 

  • Cabalska, B., Sendecka, E., Zorska, K., and Nowaczewska, I. (1994). Mild hyperphenyalaninemia detected through PKU newborn screening in Poland. Paper presented at International Symposium on Phenyketonuria: Past, Present, Future, Elsinore, Denmark.

  • Denckla, M. B. (1996). Research on executive function in a neurodevelopmental context: Application of clinical measures. Dev. Neuropsychol.12: 5-15.

    Google Scholar 

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

    Google Scholar 

  • Diamond, A., Ciaramitaro, V., Donner, E., Djali, S., and Robinson, M. B. (1994). An animal model of early-treated PKU. J. Neurosci.14: 3072-3082.

    Google Scholar 

  • Diamond, A., Prevor, M., Callendar, G., and Druin, D. P. (1997). Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monogr. Soc. Res. Child Dev.(Monogr. 252) 62(4).

    Google Scholar 

  • Fletcher, J. M. (1996). Executive functions in children: Introduction to a special series. Dev. Neuropsychol.12(1): 1-3.

    Google Scholar 

  • Folling, A. (1934). Uber ausscheidung von phenybrenztraubensaure in den harn als stoffwechselanomalie in verbindung mit imbezillitat. Hoppe-Seylers Z. Physiol. Chem.277: 169-176.

    Google Scholar 

  • Gershberg, F. B., and Shimamura, A. P. (1995). Impaired use of organizational strategies in free recall following frontal lobe damage. Neuropsychologia13: 1305-1333.

    Google Scholar 

  • Grant, D. A., and Berg, E. A. (1948). A behavioral analysis of degree of impairment and ease of shifting to new responses in a Weigl-type card sorting problem. J. Exp. Psychol.39: 404-411.

    Google Scholar 

  • Guttler, F., and Lou, H. (1986). Dietary problems of phenylketonuria: Effect on CNS transmitters and their possible role in behaviour and neuropsychological function. J. Inherited Metab. Dis. Suppl. 29: 169-177.

    Google Scholar 

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

    Google Scholar 

  • Incisa della Rochetta, A. I. (1986). Classification and recall of pictures after unilateral frontal or temporal lobectomy. Cortex22: 189-211.

    Google Scholar 

  • Incisa della Rochetta, A. I., and Milner, B. (1993). Strategic search and retrieval inhibition: The role of the frontal lobes. Neuropsychologia31: 503-524.

    Google Scholar 

  • Janowsky, J. S., Shimamura, A. P., Kritchevsky, M., and Squire, L. R. (1989). Cognitive impairment following frontal lobe damage and its relevance to human amnesia. Behav. Neurosci.103: 548-560.

    Google Scholar 

  • Jervis, G. A. (1953). Phenylpyruvic oligophrenia: Deficiency of phenylalanine oxidizing system. Proc. Soc. Exp. Biol. Med.82: 514-515.

    Google Scholar 

  • Jervis, G. A., Block, R. J., Bolling, D., and Kanze, E. (1940). Chemical and metabolic studies on phenylalanine. II. The phenylalanine content of the blood and spinal fluid in phenylpyruvic oligophrenia. J. Biol. Chem.134: 105-113.

    Google Scholar 

  • Koch, R., Azen, C., Friedman, E. G., and Williamson, M. L. (1984). Paired comparison between early treated phenylketonuria children and their matched sibling controls on intellectual and school achievement test results at eight years. J. Inherited Metab. Dis.7: 86-90.

    Google Scholar 

  • Koff, E., Boyle, P., and Pueschel, S. M. (1977). Perceptual-motor functioning in children with phenylketonuria. Am. J. Dis. Children131: 1084-1087.

    Google Scholar 

  • Krause, W., Halminski, M., McDonald, L., Dembure, P., Salco, R., Friedes, D., and Elsas, L.(1985). Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. J. Clin. Invest.75: 40-48.

    Google Scholar 

  • Levin, H. S., Culhane, K. A., Hartmann, J., Evankovich, K., Mattson, A. J., Harward, H., Ringholz, G., Ewing-Cobbs, L., and Fletcher, J. M. (1991). Developmental changes in performance on tests of purported frontal lobe functioning. Dev. Neuropsychol.7: 377-395.

    Google Scholar 

  • Levin, H. S., Fletcher, J. M., Kufera, J. A., Harward, H., Lilly, M. A., Mendelsohn, D., Bruce, D., and Eisenberg, H. M. (1996). Dimensions of cognition measured by the Tower of London and other cognitive tasks in head injured children and adolescents. Dev.Neuropsychol.12(1): 17-34.

    Google Scholar 

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

    Google Scholar 

  • Mazzocco, M. M. M., Nord, A. M., Van Doorninck, W., Greene, C. L., Kovar, C. G., and Pennington, B. F. (1994). Cognitive development among children with early-treated phenylketonuria. Dev. Neuropsychol.10: 133-151.

    Google Scholar 

  • McKean, C. M., Boggs, D. E., and Peterson, N. A. (1968). The influence of high phenylalanine and tyrosine on the concentration of essential amino acids in the brain. J. Neurochem.15: 235-241.

    Google Scholar 

  • Medical Research Council Working Party on Phenylketonuria (1993a). Phenylketonuria due to phenylalanine hydroxylase deficiency: An unfolding story. Br. Med. J.306: 115-119.

    Google Scholar 

  • Medical Research Council Working Party on Phenylketonuria (1993b). Recommendations on the dietary management of phenylketonuria. Arch. Dis. Children68(3): 426-427.

    Google Scholar 

  • Milner, B. (1964). Some effects of frontal lobectomy in man. In Warren, J. M., and Akert, K.(eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, NewYork, pp. 313-334.

    Google Scholar 

  • Milner, B. (1967). Brain mechanisms suggested by studies of the temporal lobes. In Darley, F. C. (ed.), Brain Mechanisms Underlying Speech and Language, Grune and Stratton, New York, pp. 122-145.

    Google Scholar 

  • Netley, C., Hanley, W. B., and Rudner, H. L. (1984). Phenylketonuria and its variants: Observations on intellectual functioning. Can. Med. Assoc. J.131: 751-755.

    Google Scholar 

  • Newcombe, F. (1969). Missile Wounds of the Brain, Oxford University Press, London.

    Google Scholar 

  • Nord, A. M., McCabe, L., and McCabe, E. R. B. (1988). Biochemical and nutritional status of children with hyperphenylalanemia. J. Inherited Metab. Dis.11: 431-432.

    Google Scholar 

  • Ozanne, A. E., Krimmer, H., and Murdoch, B. E. (1990). Speech and language skills in children with early treated phenylketonuria. Am. J. Ment. Retard.94: 625-632.

    Google Scholar 

  • Pandya, D. N., and Barnes, C. L. (1987). Architectural and connections of the frontal lobe.In Perecman, E. (ed.), The Frontal Lobes Revisited, IRBN Press, New York, pp. 41-72.

    Google Scholar 

  • Passler, M. A., Isaac, W., and Hynd, G. W. (1985). Neuropsychological development of behaviour attributed to frontal lobe functioning in children. Dev. Neuropsychol.1: 349-370.

    Google Scholar 

  • Pennington, B. F., Van Doorninck, W. J., McCabe, L. L., and McCabe, E. R. B. (1985). Neuropsychological deficits in early treated phenylketonuric children. Am. J. Ment. Defic.89: 467-474.

    Google Scholar 

  • Petrides, M. (1989). Frontal lobes and memory. In Boller, F., and Grafman, J. (eds.), The Handbook of Neuropsychology, Vol. 3, Elsevier, Amsterdam, pp. 75-90.

    Google Scholar 

  • Petrides, M., and Milner, B. (1982). Deficits on subject ordered tasks after frontal-and temporal-lobe lesions in man. Neuropsychologia20: 249-262.

    Google Scholar 

  • Petrides, M., Alivisatos, B., Evans, A. C., and Meyer, E. (1993). Dissociation of human middorsolateral from posterior dorsolateral frontal cortex in memory processing. Proc. Natl. Acad. Sci. USA90: 873-877.

    Google Scholar 

  • Ris, M. R., Williams, S. E., Hunt, M. M., Berry, H. K., and Leslie, N. (1994). Early-treated phenylketonuria: Adult neuropsychologic outcome. J. Pediatr.124: 388-392.

    Google Scholar 

  • Shimamura, A. P., Janowsky, J. S., and Squire, L. R. (1990). Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients. Neuropsychologia28: 803-813.

    Google Scholar 

  • Smith, I., and Beasley, M. (1989). Intelligence and behaviour in children with early treated phenylketonuria. Eur. J. Clin. Nutr.43: 1-5.

    Google Scholar 

  • Smith, I., Beasley, M. G., and Ades, A. E. (1990). Intelligence and quality of dietary treatment in phenylketonuria. Arch. Dis. Child.65: 472-478.

    Google Scholar 

  • Smith, M. L., Kates, M. H., and Vriezen, E. R. (1992). The development of frontal-lobe functions. In Segalowitz, S. J., and Rapin, I. (eds.), Handbook of Neuropsychology, Vol.7. Child Neuropsychology, pp. 309-330.

  • Smith, M. L., Klim, P., Mallozzi, E., and Hanley, W. B. (1996). A test of the dopamine specificity hypothesis in the cognitive performance of young adults with PKU. Dev. Neuropsychol.12: 327-341.

    Google Scholar 

  • Spreen, O., and Benton, A. L. (1977). Neurosensory Center Comprehensive Examination for Aphasia(NCCEA), rev. ed., Neuropsychology Laboratory, University of Victoria, Victoria.

    Google Scholar 

  • Stuss, D. T., Alexander, M. P., Palumbo, C. L., Buckle, L., Sayer, L., and Pogue, J. (1994). Organizational strategies of patients with unilateral or bilateral frontal injury in word list learning tasks. Neuropsychology8: 355-373.

    Google Scholar 

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

    Google Scholar 

  • Welsh, M. C., and Pennington, B. F. (1988). Assessing frontal lobe function in children: Views from developmental psychology. Dev. Neuropsychol.4: 199-230.

    Google Scholar 

  • Welsh, M. C., Pennington, B. F., Ozonoff, S., Rouse, B., and McCabe, E. R. R. (1990). Neuropsychology of early-treated phenylketonuria: Specific executive function deficits. Child Dev.61: 1697-1713.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada

    Mary Lou Smith & Paula Klim

  2. Department of Pediatrics, University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada

    Mary Lou Smith

  3. Department of Pediatrics, University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada

    William B. Hanley

  4. Division of Clinical Genetics, University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada

    William B. Hanley

Authors
  1. Mary Lou Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paula Klim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William B. Hanley
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, M.L., Klim, P. & Hanley, W.B. Executive Function in School-Aged Children with Phenylketonuria. Journal of Developmental and Physical Disabilities 12, 317–332 (2000). https://doi.org/10.1023/A:1009480013237

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009480013237

Search

Navigation