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Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review

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Abstract

Background

This systematic review study aims to evaluate the cognitive function of patients with mild hyperphenylalaninemia (mHPA) without treatment.

Methods

A systematic literature search was done from the 1st of May to the 30th of July in 2021 on published studies. The search strategy was ((hyperphenylalaninemia) OR (phenylketonuria) AND (cognition)). We use PubMed, Scopus, and the Web of Science databases. Studies which reported their findings regarding the cognitive function of patients with mHPA (screening serum phenylalanine > 120 and < 600 μmol/L) were included and reviewed.

Results

From initially retrieved 2805 studies, finally, 15 studies (10 on untreated patients with Phe levels below 360 μmol/L, 7 on untreated patients with Phe levels between 360 and 600 μmol/L, four 120–600 μmol/L) were selected. Most of the studies used the Wechsler Intelligence Scale for IQ evaluation, two (2/15) of them used the Stanford–Binet test and two used both tests. Four studies have reported a worse cognitive outcome compared to the control group, and in one study, relative defects in attention and working memory were reported. Other studies have reported normal IQ levels and no significant cognitive defects.

Conclusion

It is suggested that Phe levels between 120 and 360 μmol/L are generally safe. Some studies showed that untreated patients with higher levels might show some degrees of cognitive impairment. In conclusion, current knowledge is insufficient to state that treatment is not required for HPA patients to preserve their cognitive status, especially in patients with Phe levels of 360–600 μmol/L. Further studies with a larger sample size and standardized cognitive function evaluation tools are needed.

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Funding

This study was funded by Isfahan University of medical sciences with the code number 55836.

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Authors and Affiliations

  1. Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Noushin Rostampour, Rojin Chegini, Silva Hovsepian & Mahin Hashemipour

  2. Department of Pediatrics, School of Medicine, Imam Hossein Children’s Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

    Noushin Rostampour & Mahin Hashemipour

  3. Imam Hossein Children’s Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

    Silva Hovsepian

  4. Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

    Farzaneh Zamaneh

Authors
  1. Noushin Rostampour
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  2. Rojin Chegini
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  3. Silva Hovsepian
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  4. Farzaneh Zamaneh
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  5. Mahin Hashemipour
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Contributions

R. C. and F. Z. contributed to the design of the study and literature search and data collection. S. H. contributes to design and concepts, reading the final articles, manuscript revision, and approving the final submitted version. N. R. contributed to the concepts, data collection, manuscript revision, reading the final articles, and final approval. M. H. contributes to the concepts, reading the final articles, and manuscript revision. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Noushin Rostampour or Silva Hovsepian.

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Ethics approval and consent to participate

This study was accepted by Isfahan University of medical sciences' Ethics Committee with the code number of IR.MUI.MED.REC.1400.685.

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Not applicable.

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The authors declare no competing interests.

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Rostampour, N., Chegini, R., Hovsepian, S. et al. Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review. Neurol Sci 43, 5593–5603 (2022). https://doi.org/10.1007/s10072-022-06194-6

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  • DOI: https://doi.org/10.1007/s10072-022-06194-6

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