The influence of blood phenylalanine levels on neurocognitive function in adult PKU patients
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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.
KeywordsPhenylketonuria CANTAB Neurocognitive functions Phenylalanine Protein-restricted diet
Computerized Cambridge Cognition
Motor Screening Test
Stockings of Cambridge
Supplementary motor area
Spatial Working Memory
The authors wish to thank all the participants of the study.
Compliance with ethical standards
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.
Anna Bartus, Fanni Palasti, Eszter Juhasz, Erika Kiss, Erika Simonova, Csaba Sumanszki and Peter Reismann declare that they have no conflict of interest.
- Burgard P, Ullrich K, Ballhausen D, Hennermann JB, Hollak CEM, Langeveld M, Karall D, Konstantopoulou V, Maier EM, Lang F, Lachmann R, Murphy E, Garbade S, Hoffmann GF, Kölker S, Lindner M, Zschocke J (2017) Issues with European guidelines for phenylketonuria. Lancet Diabetes Endocrionol 5:681–683CrossRefGoogle Scholar
- Scriver CR, Beaudet AL, Sly WS, Valle D (1996) The metabolic and molecular bases of inherited disease, 7th edn. McGraw–Hill, New York, pp 1015–1075Google Scholar
- van Spronsen FJ, van Wegberg AM, Ahring K, Bélanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Gizewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, Trefs FK, van Rijn M, Walter JH, MacDonald A (2017) Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 5:743–756CrossRefPubMedGoogle Scholar
- Vockley J, Andersson HC, Antshel KM, Braverman NE, Burton BK, Frazier DM, Mitchell J, Smith WE, Thompson BH, Berry SA, American College of Medical Genetics and Genomics Therapeutics Committee (2014) Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med 16:188–200CrossRefPubMedGoogle Scholar