Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study

Bianca M.L. Stelten, Maria Teresa Dotti, Aad Verrips, Bülent Elibol, Tzipora C. Falik-Zaccai, Kate Hanman, Andrea Mignarri, Belina Sithole, Robert D. Steiner, Surabhi Verma, Gilad Yahalom, Tanyel Zubarioglu, Fanny Mochel, Antonio Federico

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16 Scopus citations

Abstract

Background: Cerebrotendinous xanthomatosis (CTX) is a rare, chronic, progressive, neurodegenerative disorder requiring life-long care. Patients with CTX often experience a diagnostic delay. Although early diagnosis and treatment initiation can improve symptoms and prognosis, a standardised approach to diagnosis, treatment and management of patients is not yet established. Aim: To assess expert opinion on best care practices for patients with CTX using a modified Delphi method. Methods: A multidisciplinary group of healthcare professionals with expertise in CTX responded to a 3-round online questionnaire (n = 10 in Rounds 1 and 2; n = 9 in Round 3), containing questions relating to the diagnosis, treatment, monitoring, multidisciplinary care and prognosis of patients with CTX. Determination of consensus achievement was based on a pre-defined statistical threshold of ≥ 70% Delphi panellists selecting 1–2 (disagreement) or 5–6 (agreement) for 6-point Likert scale questions, or ≥ 70% Delphi panellists choosing the same option for ranking and proportion questions. Results: Of the Round 1 (n = 22), Round 2 (n = 32) and Round 3 (n = 26) questions for which consensus was assessed, 59.1%, 21.9% and 3.8% reached consensus, respectively. Consensus agreement that genetic analyses and/or determination of serum cholestanol levels should be used to diagnose CTX, and dried bloodspot testing should facilitate detection in newborns, was reached. Age at diagnosis and early treatment initiation (at birth, where possible) were considered to have the biggest impact on treatment outcomes. All panellists agreed that chenodeoxycholic acid (CDCA) is a lifetime replacement therapy which, if initiated early, can considerably improve prognosis as it may be capable of reversing the pathophysiological process in CTX. No consensus was reached on the value of cholic acid therapy alone. Monitoring patients through testing plasma cholestanol levels and neurologic examination was recommended, although further research regarding monitoring treatment and progression of the disease is required. Neurologists and paediatricians/metabolic specialists were highlighted as key clinicians that should be included in the multidisciplinary team involved in patients’ care. Conclusions: The results of this study provide a basis for standardisation of care and highlight key areas where further research is needed to inform best practices for the diagnosis, treatment and management of patients with CTX.

Original languageEnglish
Article number353
JournalOrphanet Journal of Rare Diseases
Volume16
Issue number1
DOIs
StatePublished - 6 Aug 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Funding

This study was sponsored by Leadiant Biosciences. Coordination of the Delphi panel by Costello Medical, UK (KH, BSi, AG and DS), was funded by Leadiant Biosciences. AV, AF and MTD were paid honoraria to attend the face-to-face meeting to input on the study design. Delphi panellists did not receive funding from Leadiant Biosciences or any other sources for participation in the Delphi panel or for being authors of this manuscript. All experts who contributed as Delphi panellists are authors of this manuscript. Support for third-party writing assistance for this article, provided by Emma Warnants, MBiomedSci, Eleanor Thurtle, MChem and Katharina Strege, PhD, BSc, Costello Medical, UK, was funded by Leadiant Biosciences in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). The authors acknowledge Costello Medical, for writing and editorial assistance and Annabel Griffiths (AG), Danielle Sheard (DS) and Patsy Tomlinson (PT), Costello Medical, UK, for contributions to the conception and design of the study. This study was funded by Leadiant Biosciences Ltd (UK). The authors acknowledge Costello Medical, for writing and editorial assistance and Annabel Griffiths (AG), Danielle Sheard (DS) and Patsy Tomlinson (PT), Costello Medical, UK, for contributions to the conception and design of the study. This study was funded by Leadiant Biosciences Ltd (UK).

FundersFunder number
Costello Medical
Danielle Sheard
Leadiant Biosciences
Leadiant Biosciences Ltd

    Keywords

    • CTX
    • Cerebrotendinous xanthomatosis
    • Delphi
    • Diagnosis
    • Monitoring
    • Prognosis
    • Treatment

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