Journal of Inherited Metabolic Disease

, Volume 41, Issue 4, pp 641–646 | Cite as

Autism spectrum disorder: an early and frequent feature in cerebrotendinous xanthomatosis

  • Bianca M. L. SteltenEmail author
  • Olivier Bonnot
  • Hidde H. Huidekoper
  • Francjan J. van Spronsen
  • Peter M. van Hasselt
  • Leo A. J. Kluijtmans
  • Ron A. Wevers
  • Aad Verrips
Original Article



Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism (IEM) due to mutations in the CYP27A1 gene. The clinical picture ranges from being nearly asymptomatic in early childhood, up to severe disability at adult age. Infantile-onset diarrhea and juvenile-onset cataract are the earliest symptoms in childhood. In the current study, we evaluated the presence of autism spectrum disorder (ASD) in a large cohort of CTX patients.


We performed a retrospective patient file study in 77 genetically confirmed Dutch CTX patients to determine the frequency of ASD. In addition, we compared plasma cholestanol levels in CTX patients with and without a diagnosis of ASD and tried to establish a relation between CYP27A1 genotype and ASD.


In our CTX cohort, 10 patients (13%; nine pediatric and one adult) with ASD were identified. At the time of diagnosis of ASD, most patients only exhibited symptoms of diarrhea and/or intellectual disability without signs of cataract or neurological symptoms. No correlation was found between the presence of ASD and the level of cholestanol or CYP27A1 genotype. The behavioral problems stabilized or improved after treatment initiation with chenodeoxycholic acid (CDCA) in all pediatric patients.


We conclude that ASD is an early and probably underestimated frequent feature in CTX. Metabolic screening for CTX should be performed in patients with ASD when accompanied by diarrhea, intellectual disability, juvenile cataract, and/or neurological involvement. Early recognition allows for earlier initiation of specific treatment and will improve clinical outcome. Our results add CTX to the list of treatable IEMs associated with ASD.


Compliance with ethical standards

Conflict of interest

Olivier Bonnot received honoraria from Actelion and Orphan Europe and is a board member for Actelion and Orphan Europe.

Aad Verrips received honoraria from serving as a consultant for Sigma-Tau Pharmaceuticals, Inc., USA and Sigma-Tau Rare Disease Limited, United Kingdom.

B. M. L. Stelten, H. H. Huidekoper, F. J. van Spronsen, P. M. van Hasselt, L. A. J. Kluijtmans, and R. A. Wevers declare that they have no conflict of interest.

Informed consent

The study was done in accordance with the Helsinki Declaration and approved by the Local Ethics Committee of the Canisius Hospital Nijmegen, the Netherlands. Informed consent was obtained.

Animal rights

This article does not contain any studies with animal subjects performed by any of the authors.


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Copyright information

© SSIEM 2017

Authors and Affiliations

  • Bianca M. L. Stelten
    • 1
    Email author
  • Olivier Bonnot
    • 2
  • Hidde H. Huidekoper
    • 3
  • Francjan J. van Spronsen
    • 4
  • Peter M. van Hasselt
    • 5
  • Leo A. J. Kluijtmans
    • 6
  • Ron A. Wevers
    • 6
  • Aad Verrips
    • 1
  1. 1.Department of NeurologyCanisius Wilhelmina HospitalNijmegenThe Netherlands
  2. 2.Child and Adolescent Psychiatry DepartmentUniversity Hospital of NantesNantesFrance
  3. 3.Department of Pediatrics, Center for Lysosomal and Metabolic DiseasesErasmus Medical Center-University HospitalRotterdamThe Netherlands
  4. 4.Division of Metabolic DiseasesBeatrix Children’s Hospital, University Medical Center Groningen, University of GroningenGroningenThe Netherlands
  5. 5.Department of Metabolic DisordersUniversity Medical Center UtrechtUtrechtThe Netherlands
  6. 6.Department of Laboratory Medicine, Translational Metabolic LaboratoryDonders Institute for Brain, Cognition and Behaviour, Radboud University Medical CenterNijmegenThe Netherlands

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