Cerebrotendinous Xanthomatosis

Cerebrotendinous Xanthomatosis

National Organization for Rare Disorders, Inc.


It is possible that the main title of the report Cerebrotendinous Xanthomatosis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • CTX
  • cerebral cholesterinosis
  • sterol 27-hydroxylase deficiency

Disorder Subdivisions

  • None

General Discussion

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive genetic disorder caused by an abnormality in the CYP27A1 gene, resulting in a deficiency of the mitochondrial enzyme sterol 27-hydroxylase. The lack of this enzyme prevents cholesterol from being converted into a bile acid called chenodexoycholic acid. Cholestanol deposits accumulate in the nerve cells and membranes, and cause damage to the brain, spinal cord, tendons, lens of the eye and arteries. Affected individuals experience cataracts in childhood, and benign, fatty tumors (xanthomas) of the tendons during adolescence. This leads to progressive neurologic problems in adulthood such as paralysis, ataxia and dementia. Coronary heart disease is common.


The first symptoms of CTX may be chronic diarrhea in infancy. Cataracts in the first decade of life are the first symptom in about 75% of those affected. Xanthomas appear in the second or third decade and can be located in the Achilles tendon, extensor tendons of the elbow and hand, and knee. Most affected individuals experience a decline in mental function beginning at puberty, but some show impairment beginning in childhood. Dementia and a slow loss in mental function occur in more than half of those affected. Symptoms such as seizures, behavioral changes, hallucinations, agitation, aggression, depression, and suicidal tendencies are common. Spasticity almost always occurs between 20-30 years of age.


CTX is an autosomal recessive genetic condition caused by an abnormality in the CYP27A1 gene, resulting in a deficiency of the mitochondrial enzyme sterol 27-hydroxylase. The lack of this enzyme prevents cholesterol from being converted into the bile acid chenodeoxycholic acid that helps the intestine absorb fats. Cholestanol deposits accumulate and cause damage to the brain, spinal cord, tendons, lens of the eye and arteries.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

The prevalence of CTX is not known. Affected individuals have been reported in the USA, Israel, Italy, Japan, the Netherlands, Belgium, Brazil, Canada, France, Iran, Norway, Tunisia, Spain, China and Sweden.

Standard Therapies


CTX is diagnosed by performing several biochemical tests on blood and urine. Cholestanol concentration in blood plasma and in tissues is high, plasma cholesterol concentration is normal to low, and the concentration of bile alcohols in bile, urine and plasma is increased. Molecular genetic testing for the abnormal CYP27A1 gene is available on a research basis only.


Long-term treatment with chenodeoxycholic acid (CDCA) can block the production of cholestanol. CDCA can stop the progression of disease symptoms and may lead to improvement in some affected individuals. HMG-CoA reductase inhibitors are sometimes used in combination with CDCA because they also lower both cholesterol and cholestanol concentrations to avoid coronary heart disease.

In October 2009, the Food and Drug Administration approved Chenodal as a treatment for CTX. This drug is marketed in the U.S. By Manchester Pharmaceuticals, Inc. A patient assistance program, the Chenodal Total Care Program, may help patients who need financial assistance obtain this drug. The number for the program is 866 758 7068.

Cataract surgery is usually necessary before 50 years of age.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


A Phase II clinical trial is in progress at the Oregon Health and Science University. The purpose is to help evaluate the drugs lovastatin and chenodeoxycholic acid, and cholesterol- and cholestanol-free diets, as therapies for people with CTX. For information, contact Sonja Connor at Connors@ohsu.edu or (503) 494-7775.



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Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci. 2006;27(2):143-9.

Inglese M, DeStefano N, Pagani E, et al. Quantification of brain damage in cerebrotendinous xanthomatoisis with magnetization transfer MR imaging. AJNR Am J Neuroradiol 2003;24:495-500.

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Mignarri A, Rossi S, Ballerini M, et al. Clinical relevance and neurophysiological correlates of spasticity in cerebrotendinous xanthomatosis.[published online ahead of print November 21, 2010] J Neurol. 2010. http://www.ncbi.nlm.nih.gov/pubmed/21104094. Accessed March 15, 2011.

Federico A, Dotti MT, Gallus GN. (Updated 11/16/10). Cerebrotendinous Xanthomatosis. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2011. Available at http://www.genetests.org. Accessed 3/15/11.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Cerebrotendinous Xanthomatosis. Entry No: 213700. Last Updated January 7, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed March 15, 2011.


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For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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