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Review
. 2025 Apr 2;20(1):156.
doi: 10.1186/s13023-025-03686-4.

The relationship between adult phenylketonuria and the cardiovascular system - insights into mechanisms and risks

Yann Dos Santos  1 , Friedrich Trefz  2 , Maria Giżewska  3 , Annemiek M J van Wegberg  4 , Bruno Lefort  5 , François Labarthe  5 , Francjan van Spronsen  4 , François Maillot  6   7
Affiliations
Review

The relationship between adult phenylketonuria and the cardiovascular system - insights into mechanisms and risks

Yann Dos Santos et al. Orphanet J Rare Dis. .

Abstract

Studies in adults with PKU have mainly focused on the neuropsychiatric complications that may arise in individuals who are unable to maintain the recommended lifetime diet. Some recent epidemiological studies suggest to consider other complications. As such, cardiovascular (CV) issues have been the subject of few studies to date. The aim of this review is to gather and discuss data from the literature on the traditional risks of CV complications in PKU, a potential CV phenotype in this population and the various non-traditional risks and potential associated mechanisms. The reported prevalence of comorbidities suggests an increased risk of CV complications in adults with PKU, mostly in late-diagnosed patients. Studies about a specific CV phenotype associated with PKU are suggestive, although further studies are needed. The data on oxidative stress in this population are consistent and confirm an increased CV risk. Regarding other potential mechanisms, it is not possible to conclude whether adult PKU patients have low grade inflammation, dyslipidemia, kidney impairment or if they have hyperhomocysteinemia. It would be of interest to measure potential biomarker associated with CV complications, such as homocysteine, asymmetric dimethylarginine and kynurenines (quinolic acid).

Keywords: Adults; Cardiovascular disease; Phenylketonuria.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart showing article selection process. Based on title, articles not in English or dealing solely with children or the maternal syndrome of PKU were excluded. The remaining articles were then selected by reading the abstract or the article itself, when the abstract did not allow us to conclude whether the article was relevant to the subject in question. The remaining articles have been included in the review
Fig. 2
Fig. 2
Summary of results concerning traditional CVD risk and potential associated mechanisms. Heart image comes from BioRender.com
See this image and copyright information in PMC

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