The safety and effectiveness of chenodeoxycholic acid treatment in patients with cerebrotendinous xanthomatosis: two retrospective cohort studies

Verrips, Aad; Dotti, Maria Teresa; Mignarri, Andrea; Stelten, Bianca M L; Verma, Sue; Federico, Antonio

doi:10.1007/s10072-019-04169-8

Cited by 31 publications

(29 citation statements)

References 17 publications

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“…In this patient cholestasis developed after 6 weeks of treatment and liver enzymes returned to normal values within 3 months after cessation of CDCA. It must be noticed that jaundice with spontaneous resolution can be a manifestation of the disease, as in our patient, so that the relationship with the treatment is uncertain, in this patient hepatitis did not recur on re-challenge with CDCA ( 4 , 18 ). Both CDCA and CA have been shown safe during pregnancy ( 5 , 11 , 27 , 28 ).…”

Section: Discussionmentioning

confidence: 61%

“…The estimated prevalence of CTX is 1:50.000 ( 4 ), with high variability among patients regarding age of onset and type of symptoms, since clinical manifestations appear along with the progressive accumulation of toxic metabolites ( 5 ). In infancy CTX may cause cholestatic jaundice, that usually spontaneously resolves ( 6 , 7 ), so that the disease may be overlooked.…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Early Treatment With Chenodeoxycholic Acid in Cerebrotendinous Xanthomatosis Presenting as Neonatal Cholestasis

et al. 2020

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Background: Cerebrotendinous xanthomatosis (CTX) is an inborn disorder of bile acid synthesis which causes progressive accumulation of toxic metabolites in various organs, particularly in brain and tendons. Most cases are diagnosed and treated in the second or third decade of life, when neurological involvement appears. We describe a case of CTX presenting as neonatal cholestasis. Results: The child presented cholestasis at 2 months of life. In the following months jaundice slowly disappeared, with a normalization of bilirubin and aminotransferases, respectively, at 6 and 8 months. A LC-Mass Spectrometry of the urines showed the presence of cholestanepentols glucuronide, which led to the suspicion of cerebrotendinous xanthomatosis. The diagnosis was confirmed by the dosage of cholestanol in serum and the molecular genetic analysis of the CYP27A1 gene. Therapy with chenodeoxycholic acid (CDCA) was started at 8 months and is still ongoing. The child was monitored for 13 years by dosage of serum cholestanol and urinary cholestanepentols. A strictly biochemical and neurological follow up was performed and no sign of neurological impairment was observed. Conclusions: Prompt diagnosis and treatment of CTX presenting as neonatal cholestasis may prevent further neurological impairment.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Case Report: Early Treatment With Chenodeoxycholic Acid in Cerebrotendinous Xanthomatosis Presenting as Neonatal Cholestasis

et al. 2020

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“…As described by many, the importance of diagnosing this neurodegenerative condition is because it is potentially treatable. The treatment can reverse, stabilize, or prevent accumulation of cholestanol in CNS slowing the development or stopping the progression of neurological symptoms [ 5 , 9 ]. A cross-sectional observational study demonstrated worse outcome and significant limitation in ambulation and cognition in patients with CTX diagnosed after the age of 25 despite treatment with chenodeoxycholic acid [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

2021

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Background Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability. Methods A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years. Results Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia. Conclusion A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.

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“…All patients were evaluated at visits by one of the authors (AV) in a systematic manner and data recorded in the medical chart. The patients reported here were included in previous publications focussing on other clinical aspects of CTX 2,12 …”

Section: Methodsmentioning

confidence: 99%

Cerebrotendinous xanthomatosis‐associated diarrhea and response to chenodeoxycholic acid treatment

2020

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Background In patients with cerebrotendinous xanthomatosis (CTX), chronic diarrhea is one of the earliest and main symptoms of the disease. In the current study, we evaluated the characteristics of the diarrhea and its response to chenodeoxycholic acid (CDCA) therapy in a cohort of Dutch CTX patients. Methods We performed a retrospective review of medical records for 33 genetically confirmed CTX patients, and abstracted the characteristics of the diarrhea and the response to CDCA therapy (15 mg/kg/day up to 750 mg/day). The Bristol Stool Scale (BSS) was used for qualitative characterization of the stool. Results Twenty‐five patients had diarrhea documented at baseline (76%). Of these patients, 10 had diarrhea rated as 6 (fluffy pieces with ragged edges, a mushy stool), and 6 had diarrhea rated as 7 (watery, no solid pieces, entirely liquid) using the BSS. In 10 patients for whom data were recorded, the median stool frequency at baseline was 3 per day (range 2‐6 per day). The response rate with CDCA for diarrhea resolution was 100% based on at least one post‐baseline visit without diarrhea and 95% as assessed at the first post‐baseline visit. In 68% of cases resolution was complete and sustained as no episodes of diarrhea were documented for follow‐up periods as long as 25 years. Conclusions Chronic diarrhea persisting for years without spontaneous remission is a common feature of CTX at diagnosis. Chenodeoxycholic acid is an effective treatment for symptomatic relief of diarrhea in patients with CTX.

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The safety and effectiveness of chenodeoxycholic acid treatment in patients with cerebrotendinous xanthomatosis: two retrospective cohort studies

Cited by 31 publications

References 17 publications

Case Report: Early Treatment With Chenodeoxycholic Acid in Cerebrotendinous Xanthomatosis Presenting as Neonatal Cholestasis

Case Report: Early Treatment With Chenodeoxycholic Acid in Cerebrotendinous Xanthomatosis Presenting as Neonatal Cholestasis

Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

Cerebrotendinous xanthomatosis‐associated diarrhea and response to chenodeoxycholic acid treatment

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