Neurological manifestations in adults with phenylketonuria: new cases and review of the literature

  • Paul Jaulent
  • Sybil CharriereEmail author
  • François Feillet
  • Claire Douillard
  • Alain Fouilhoux
  • Stéphane Thobois
Original Communication



Phenylketonuria (PKU) is a rare autosomal recessive disease characterised by high plasma phenylalanine levels inducing, if untreated, serious neurological manifestations in children but also, rarely, in adults who stopped their diet. The objective of the study was to describe the neurological manifestations observed in adults with PKU.


We analysed cases reported in French reference centres for inborn errors of metabolism and cases already reported in the literature.


We report 8 new cases of neurological manifestations and 22 cases in the literature, which occurred in adult PKU patients, associated with chronic or rapid increase of phenylalanine levels, mostly when strict low-phenylalanine diet was stopped early in life. Neurological symptoms consisted in cerebellar ataxia, tremor, brisk reflexes, visual loss, sensory manifestations, and/or headaches. Visual loss was more frequent in the new cases (4/8) of the present series than in the literature (4/22). These neurological complications were associated with leucopathy on brain magnetic resonance imaging (27/29). The start of a low-phenylalanine diet improved or fully reversed neurological manifestations, even in patients with late diagnosis during adulthood.


Neurological manifestations can complicate PKU in adult patients with elevated phenylalanine levels, after long or short period of diet discontinuation. Neurologists should be aware of this diagnosis, and measure phenylalaninemia in case of neurological symptoms associated with non-specific leucopathy on brain MRI. PKU patients should be systematically encouraged to continue their diet and their medical follow-up to avoid neurological complications.


Adult phenylketonuria Neurological symptoms Brain MRI Leucopathy 


Author contributions

All authors contributed to the study conception and design. Data collection was performed by PJ, SC, FF, and CD. Analyses of data were performed by PJ and SC. The first draft of the manuscript was written by PJ, SC, and TB, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflicts of interest

The authors have no conflict of interest related to this article.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Neurologie CBron CedexFrance
  2. 2.Hospices Civils de Lyon, Hôpital Cardiovasculaire Louis Pradel, Fédération D’endocrinologie, Maladies métaboliques, diabète Et Nutrition, Groupement Hospitalier EstBron CedexFrance
  3. 3.INSERM U1060, Laboratoire Carmen, Université Lyon 1, INRA U1235, INSA de LyonVilleurbanneFrance
  4. 4.CENS, Centre de Recherche en Nutrition Humaine Rhône AlpesOullins CedexFrance
  5. 5.Université Lyon 1 Claude Bernard, Faculté de médecine Lyon ESTLyonFrance
  6. 6.Hospices Civils de Lyon, Centre de référence Des Maladies héréditaires du métabolisme de Lyon, Groupement Hospitalier EstBron CedexFrance
  7. 7.CHU de Nancy, Hôpitaux de Brabois, Centre de référence Des Maladies héréditaires du métabolisme de NancyVandoeuvre-les NancyFrance
  8. 8.Centre Hospitalier Régional Universitaire de Lille, Hopital Claude Huriez, Service D’Endocrinologie-Diabétologie-Métabolisme, Hopital HuriezLilleFrance
  9. 9.CNRS, Institut Des Sciences Cognitives Marc Jeannerod, UMR 5229BronFrance

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