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The influence of blood phenylalanine levels on neurocognitive function in adult PKU patients

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Abstract

It is well known that hyperphenylalaninemia caused by phenylketonuria (PKU) negatively influences cognitive performance. Several tests have been used to study these functions. Until now, no universal, optimal tool has been developed for detecting PKU-caused brain dysfunctions. Using computerized neuropsychological tests during daily routine would be helpful for screening subclinical brain deficits in adult PKU patients. In a monocentric, cross-sectional study, adult patients with PKU (n = 46; median age = 29.5 years; female/male ratio = 21/25) were tested with the computerized Cambridge Cognition (CANTAB) test measuring neurocognitive functions. Patients were divided into two groups: The “on diet” group included patients whose blood Phe-level was under 600 μmol/l (n = 20), and the “loose diet” group included patients whose blood Phe-level was above 600 μmol/l (n = 26) at the examination time. The results of the PKU-affected individuals were compared with a healthy control group (n = 31; median age = 25 years; female/male ratio = 11/20). Compared with the control group, PKU patients had significantly worse test results in memory, problem-solving skills, and strategy. However, there were no significant differences in response speed or initial thinking time. There was no correlation between the blood Phe-level, tyrosine (Tyr)-level or Phe/Tyr ratio and the different cognitive test results. There were no significant differences in test results between the two PKU subgroups. Several cognitive functions measured by CANTAB are negatively influenced by hyperphenylalaninemia in adult PKU patients. However, response speed and initial thinking time were not impaired as seriously as other functions. Patients with lower Phe-levels failed to achieve better test results than patients whose Phe-levels were notably elevated.

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Abbreviations

CANTAB:

Computerized Cambridge Cognition

ETPK:

Early-treated PKU

IQ:

Intelligence quotient

MOT:

Motor Screening Test

PAH:

Phenylalanine hydroxylase

Phe:

Phenylalanine

PKU:

Phenylketonuria

PMA:

Premotor area

μmol:

Micromol

SOC:

Stockings of Cambridge

SMA:

Supplementary motor area

SWM:

Spatial Working Memory

Tyr:

Tyrosine

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Acknowledgements

The authors wish to thank all the participants of the study.

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Author notes

  1. A. Bartus and F. Palasti contributed equally to this work.

Authors and Affiliations

  1. 2nd Department of Internal Medicine, Semmelweis University, Szentkirályi Street 46, Budapest, H-1088, Hungary

    A. Bartus, F. Palasti, E. Juhasz, Cs. Sumanszki & P. Reismann

  2. 1st Department of Pediatrics, Semmelweis University, Bókay János u. 53-54, Budapest, H-1083, Hungary

    E. Kiss & E. Simonova

Authors
  1. A. Bartus
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  2. F. Palasti
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  3. E. Juhasz
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  4. E. Kiss
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  5. E. Simonova
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  6. Cs. Sumanszki
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  7. P. Reismann
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Corresponding author

Correspondence to P. Reismann.

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Ethical approval and consent to participate

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Semmelweis University) and with the Helsinki Declaration of 1975. The study was approved by the Hungarian ethical committee ETT TUKEB (Medical Research Council Scientific and Research Committee): reference number: 5075-2/2014/EKU). An informed consent was obtained from all patients prior to enrollment in the study.

Competing interest

Anna Bartus, Fanni Palasti, Eszter Juhasz, Erika Kiss, Erika Simonova, Csaba Sumanszki and Peter Reismann declare that they have no conflict of interest.

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Bartus, A., Palasti, F., Juhasz, E. et al. The influence of blood phenylalanine levels on neurocognitive function in adult PKU patients. Metab Brain Dis 33, 1609–1615 (2018). https://doi.org/10.1007/s11011-018-0267-6

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  • DOI: https://doi.org/10.1007/s11011-018-0267-6

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