Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis

Paul Duell, Gerald Salen, Florian S. Eichler, Andrea De Barber, Sonja L. Connor, Lise Casaday, Suman Jayadev, Yasushi Kisanuki, Patamaporn Lekprasert, Mary J. Malloy, Ritesh A. Ramdhani, Paul E. Ziajka, Joseph Quinn, Kimmy G. Su, Andrew S. Geller, Margaret R. Diffenderfer, Ernst J. Schaefer

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to defective sterol 27-hydroxylase causing a lack of chenodeoxycholic acid (CDCA) production and high plasma cholestanol levels. Objectives: Our objective was to review the diagnosis and treatment results in 43 CTX cases. Methods: We conducted a careful review of the diagnosis, laboratory values, treatment, and clinical course in 43 CTX cases. Results: The mean age at diagnosis was 32 years; the average follow-up was 8 years. Cases had the following conditions: 53% chronic diarrhea, 74% cognitive impairment, 70% premature cataracts, 77% tendon xanthomas, 81% neurologic disease, and 7% premature cardiovascular disease. The mean serum cholesterol concentration was 190 mg/dL; the mean plasma cholestanol level was 32 mg/L (normal <5.0 mg/L), which decreased to 6.0 mg/L (−81%) with CDCA therapy generally given as 250 mg orally 3 times daily. Of those tested on treatment, 63% achieved cholestanol levels of <5.0 mg/L; 91% had normal liver enzyme levels; none had significant liver problems after dose adjustment. Treatment improved symptoms in 57% at follow-up, but 20% with advanced disease continued to deteriorate. In the United States, CDCA has been approved for gallstone dissolution, but not for CTX despite long-term efficacy and safety data. Conclusions: Health care providers seeing young patients with tendon xanthomas and relatively normal cholesterol levels, especially those with cataracts and learning problems, should consider the diagnosis of CTX so they can receive treatment. CDCA should receive regulatory approval to facilitate therapy for the prevention of the complications of the disease.

Original languageEnglish (US)
JournalJournal of Clinical Lipidology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Cerebrotendinous Xanthomatosis
Chenodeoxycholic Acid
Cholestanol
Xanthomatosis
Tendons
Cataract
Therapeutics
Cholestanetriol 26-Monooxygenase
Cholesterol
Social Adjustment
Clinical Laboratory Techniques
Liver
Gallstones
Nervous System Diseases
Health Personnel
Diarrhea
Cardiovascular Diseases
Learning
Safety

Keywords

  • Bile acid
  • Cerebrotendinous xanthomatosis
  • Chenodeoxycholic acid
  • Cholestanol
  • Cholesterol biosynthesis
  • CYP27A1 gene
  • Neurologic abnormality
  • Xanthomas

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

Duell, P., Salen, G., Eichler, F. S., De Barber, A., Connor, S. L., Casaday, L., ... Schaefer, E. J. (Accepted/In press). Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis. Journal of Clinical Lipidology. https://doi.org/10.1016/j.jacl.2018.06.008

Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis. / Duell, Paul; Salen, Gerald; Eichler, Florian S.; De Barber, Andrea; Connor, Sonja L.; Casaday, Lise; Jayadev, Suman; Kisanuki, Yasushi; Lekprasert, Patamaporn; Malloy, Mary J.; Ramdhani, Ritesh A.; Ziajka, Paul E.; Quinn, Joseph; Su, Kimmy G.; Geller, Andrew S.; Diffenderfer, Margaret R.; Schaefer, Ernst J.

In: Journal of Clinical Lipidology, 01.01.2018.

Research output: Contribution to journalArticle

Duell, P, Salen, G, Eichler, FS, De Barber, A, Connor, SL, Casaday, L, Jayadev, S, Kisanuki, Y, Lekprasert, P, Malloy, MJ, Ramdhani, RA, Ziajka, PE, Quinn, J, Su, KG, Geller, AS, Diffenderfer, MR & Schaefer, EJ 2018, 'Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis', Journal of Clinical Lipidology. https://doi.org/10.1016/j.jacl.2018.06.008
Duell, Paul ; Salen, Gerald ; Eichler, Florian S. ; De Barber, Andrea ; Connor, Sonja L. ; Casaday, Lise ; Jayadev, Suman ; Kisanuki, Yasushi ; Lekprasert, Patamaporn ; Malloy, Mary J. ; Ramdhani, Ritesh A. ; Ziajka, Paul E. ; Quinn, Joseph ; Su, Kimmy G. ; Geller, Andrew S. ; Diffenderfer, Margaret R. ; Schaefer, Ernst J. / Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis. In: Journal of Clinical Lipidology. 2018.
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abstract = "Background: Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to defective sterol 27-hydroxylase causing a lack of chenodeoxycholic acid (CDCA) production and high plasma cholestanol levels. Objectives: Our objective was to review the diagnosis and treatment results in 43 CTX cases. Methods: We conducted a careful review of the diagnosis, laboratory values, treatment, and clinical course in 43 CTX cases. Results: The mean age at diagnosis was 32 years; the average follow-up was 8 years. Cases had the following conditions: 53{\%} chronic diarrhea, 74{\%} cognitive impairment, 70{\%} premature cataracts, 77{\%} tendon xanthomas, 81{\%} neurologic disease, and 7{\%} premature cardiovascular disease. The mean serum cholesterol concentration was 190 mg/dL; the mean plasma cholestanol level was 32 mg/L (normal <5.0 mg/L), which decreased to 6.0 mg/L (−81{\%}) with CDCA therapy generally given as 250 mg orally 3 times daily. Of those tested on treatment, 63{\%} achieved cholestanol levels of <5.0 mg/L; 91{\%} had normal liver enzyme levels; none had significant liver problems after dose adjustment. Treatment improved symptoms in 57{\%} at follow-up, but 20{\%} with advanced disease continued to deteriorate. In the United States, CDCA has been approved for gallstone dissolution, but not for CTX despite long-term efficacy and safety data. Conclusions: Health care providers seeing young patients with tendon xanthomas and relatively normal cholesterol levels, especially those with cataracts and learning problems, should consider the diagnosis of CTX so they can receive treatment. CDCA should receive regulatory approval to facilitate therapy for the prevention of the complications of the disease.",
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AU - Salen, Gerald

AU - Eichler, Florian S.

AU - De Barber, Andrea

AU - Connor, Sonja L.

AU - Casaday, Lise

AU - Jayadev, Suman

AU - Kisanuki, Yasushi

AU - Lekprasert, Patamaporn

AU - Malloy, Mary J.

AU - Ramdhani, Ritesh A.

AU - Ziajka, Paul E.

AU - Quinn, Joseph

AU - Su, Kimmy G.

AU - Geller, Andrew S.

AU - Diffenderfer, Margaret R.

AU - Schaefer, Ernst J.

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