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

Orphanet Journal of Rare Diseases

Kate Hanman¹  Belina Sithole²  Maria Teresa Dotti³  Antonio Federico⁴  Aad Verrips⁵  Bianca M. L. Stelten⁶  Tanyel Zubarioglu⁷  Bülent Elibol⁸  Tzipora C. Falik-Zaccai⁹  Surabhi Verma^1,10  Fanny Mochel^1,11  Gilad Yahalom^1,12  Andrea Mignarri^1,13  Robert D. Steiner^1,14 

[1] Costello Medical, London, UK;Costello Medical, Manchester, UK;Department of Medicine, Surgery and Neurosciences, Medical School, University of Siena and UO Clinical Neurology and Neurometabolic Diseases, AOU Senese, Siena, Italy;Department of Medicine, Surgery and Neurosciences, Medical School, University of Siena, Siena, Italy;Department of Neurology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands;Department of Neurology, Catharina Hospital, Eindhoven, The Netherlands;Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey;Hacettepe University Medical Faculty Hospital, Ankara, Turkey;Institute of Human Genetics, Galilee Medical Center, Naharia, Israel;The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel;Leadiant Biosciences Ltd., London, UK;Reference Center for Adult Neurometabolic Diseases, Department of Genetics, La Pitié-Salpêtrière University Hospital, Paris, France;Shaare Zedek Medical Center, Jerusalem, Israel;Sheba Medical Center, Ramat Gan, Israel;UO Clinical Neurology and Neurometabolic Diseases, AOU Senese, Siena, Italy;University of Wisconsin School of Medicine and Public Health, Madison, WI, USA;Marshfield Clinic Health System, Marshfield, WI, USA;

关键词: Cerebrotendinous xanthomatosis;    CTX;    Delphi;    Diagnosis;    Treatment;    Prognosis;    Monitoring;   

DOI  :  10.1186/s13023-021-01980-5

来源: Springer

【 摘 要 】

BackgroundCerebrotendinous 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.AimTo assess expert opinion on best care practices for patients with CTX using a modified Delphi method.MethodsA 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.ResultsOf 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.ConclusionsThe 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.

【 授权许可】

CC BY