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

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.

Keywords: CTX; Cerebrotendinous xanthomatosis; Delphi; Diagnosis; Monitoring; Prognosis; Treatment.

Fig. 1

Delphi study design. *Total number of questions asked. For some Likert scale questions, multiple options were given, with each analysed separately to assess consensus (e.g. “During the early stages of treatment, paediatric patients should be monitored for the types of symptoms listed below 1–2 times per year. Symptoms: Central and peripheral nervous system; Ocular system; Enterohepatic system; Cognitive performance [e.g. learning difficulties]; Cardiovascular system; Skeletal system; Pulmonary system”, where consensus was assessed separately for each symptom). †For each round, questionnaires were left open for responses in SurveyMonkey until analyses of the results began