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

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

Journal: Journal of clinical lipidology 2019;12(5):1169-1178

PMID: 30017468

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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.

Address: Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.; Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.; Department of Neurology, Massachusetts General Hospital for Children, Boston, MA, USA.; Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR, USA.; Department of Neurology, University of South Florida, Tampa, FL, USA.; Department of Neurology, Western Medical Center, University of Washington, Seattle, WA, USA.; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.; Division of Endocrinology, Einstein Medical Center, Philadelphia, PA, USA.; Division of Endocrinology, University of California San Francisco Medical Center, San Francisco, CA, USA.; Department of Neurology, New York University Medical Center, New York, NY, USA.; Florida Lipid Institute, Winter Park, FL, USA.; Department of Neurology, Oregon Health and Science University, Portland, OR, USA.; Department of Medicine, University of Washington, Seattle, WA, USA.; Boston Heart Diagnostics, Framingham, MA, USA; Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.; Boston Heart Diagnostics, Framingham, MA, USA; The Dyslipidemia Foundation, Natick, MA, USA.; Boston Heart Diagnostics, Framingham, MA, USA; Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; The Dyslipidemia Foundation, Natick, MA, USA. Electronic address: [email protected].

DOI: 10.1016/j.jacl.2018.06.008

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MeSH Terms: Adult, Child, Female, Humans, Male, Middle Aged, Treatment Outcome, Xanthomatosis, Cerebrotendinous, Young Adult