Journal of Inherited Metabolic Disease

, Volume 39, Issue 1, pp 75–83 | Cite as

Evaluation of cholesterol metabolism in cerebrotendinous xanthomatosis

  • Andrea Mignarri
  • Alessandro Magni
  • Marina Del Puppo
  • Gian Nicola Gallus
  • Ingemar Björkhem
  • Antonio Federico
  • Maria Teresa Dotti
Original Article



Cerebrotendinous xanthomatosis (CTX) is a treatable bile acid disorder caused by mutations of CYP27A1. The pathogenesis of neurological damage has not been completely explained. Oral chenodeoxycholic acid (CDCA) can lead to clinical stabilization, but in a subgroup of patients the disease progresses despite treatment. In the present study, we aimed at clarifying cholesterol metabolism abnormalities and their response to CDCA treatment, in order to identify reliable diagnostic and prognostic markers and understand if differences exist between stable patients and those with neurological progression.


We enrolled 19 untreated CTX patients and assessed serum profile of bile acids intermediates, oxysterols, cholesterol, lathosterol, and plant sterols. Then we performed a long-term follow up during CDCA therapy, and compared biochemical data with neurological outcome.


We observed increase of cholestanol, 7α-hydroxy-4-cholesten-3-one (7αC4), lathosterol, and plant sterols, whereas 27-hydroxycholesterol (27-OHC) was extremely low or absent. CDCA treatment at a daily dose of 750 mg normalized all biochemical parameters except for 7αC4 which persisted slightly higher than normal in most patients, and 27-OHC which was not modified by therapy. Biochemical evaluation did not reveal significant differences between stable and worsening patients.


Cholestanol and 7αC4 represent important markers for CTX diagnosis and monitoring of therapy. Treatment with CDCA should aim at normalizing serum 7αC4 as well as cholestanol, since 7αC4 better mirrors 7α-hydroxylation rate and is thought to be correlated with cholestanol accumulation in the brain. Assessment of serum 27-OHC is a very good tool for biochemical diagnosis at any stage of disease. Lathosterol and plant sterols should be considered as additional markers for diagnosis and monitoring of therapy. Further studies including long-term assessment of bile acid intermediates in cerebrospinal fluid are needed in patients who show clinical progression despite treatment.


Bile Acid Expand Disability Status Scale Cholic Acid Plant Sterol Expand Disability Status Scale Score 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethic Guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Conflict of interest



Andrea Mignarri, Alessandro Magni, Marina Del Puppo, Gian Nicola Gallus, Ingemar Björkhem, Antonio Federico, and Maria Teresa Dotti declare no funding.


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Copyright information

© SSIEM 2015

Authors and Affiliations

  • Andrea Mignarri
    • 1
  • Alessandro Magni
    • 2
  • Marina Del Puppo
    • 2
  • Gian Nicola Gallus
    • 1
  • Ingemar Björkhem
    • 3
  • Antonio Federico
    • 1
  • Maria Teresa Dotti
    • 1
  1. 1.Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and NeurosciencesUniversity of SienaSienaItaly
  2. 2.Department of Health Sciences, Medical SchoolUniversity of Milano-BicoccaMilanoItaly
  3. 3.Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska InstituteKarolinska University HospitalHuddingeSweden

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