Cerebrotendinous Xanthomatosis Fast Facts

(CTX) is a disorder in which the body cannot properly break down fatty compounds called cholesterols. As a result, cholesterols accumulate in the brain and other tissues, leading to a wide range of symptoms.

The first symptoms of CTX often appear in infancy, but more severe complications develop much later if the disorder is left untreated.

Symptoms of CTX include diarrhea, cataracts, and intellectual impairment.

Treatment is usually effective at slowing or stopping the progression of CTX.

United Brain Association

The first symptoms of CTX often appear in infancy, but more severe complications develop much later if the disorder is left untreated.

What is Cerebrotendinous Xanthomatosis?

Cerebrotendinous Xanthomatosis (CTX) is a disorder characterized by the body’s inability to break down fatty compounds called cholesterols. As a result, the compounds accumulate in the brain, spinal cord, arteries, tendons, and eyes, causing various symptoms.

CTX symptoms often appear first in infancy, and the progression of symptoms and complications varies widely from case to case.

Symptoms of CTX

Symptoms of CTX in infants and young children may include:

  • Chronic diarrhea
  • Cataracts
  • Bone fractures caused by brittle bones

Symptoms in adolescents and young adults can include:

  • Intellectual impairments
  • Fatty, benign tumors in tendons
  • Rigid muscles
  • Involuntary muscle movements
  • Depression
  • Agitation or aggression
  • Hallucinations
  • Dementia

What Causes Cerebrotendinous Xanthomatosis?

CTX is caused by abnormal changes (mutations) in the CYP27A1 gene. This gene carries instructions for making an enzyme vital in converting cholesterols into bile acids, chemicals used by the body to digest fats. However, the mutations interfere with the production of the enzyme, leading to an abnormal accumulation of cholesterol. As cholesterol accumulates, it damages cells in various parts of the body, resulting in the symptoms of CTX.

Is Cerebrotendinous Xanthomatosis Hereditary?

CTX is an inherited disorder. The mutations that cause it can be passed from parents to their children.

CYP27A1 mutations are inherited in an autosomal recessive pattern. This means that a child must inherit two copies of the disorder-causing gene mutation, one from each parent, to develop the condition. A parent who carries only one copy of the CYP27A1 mutation will usually show no symptoms but may pass the mutation to their children. Two parents who each carry the mutation have a 25 percent chance of having an affected child with each pregnancy. Fifty percent of their pregnancies will produce a carrier child. Twenty-five percent of the time, their child will not inherit a mutated CYP27A1 gene, meaning they will not have the disorder or be able to pass on the mutation to their children.

How Is Cerebrotendinous Xanthomatosis Detected?

Early detection of CTX is crucial because the most severe long-term complications of the disorder typically begin to emerge in childhood. When treated, these complications can often be prevented or lessened.

Early signs of hydranencephaly may include:

  • Chronic diarrhea
  • Problems with liver function
  • Cataracts
  • Impaired intellectual development

How Is Cerebrotendinous Xanthomatosis Diagnosed?

The diagnostic process for CTX varies depending on the age of the patient. In infants, analysis of the urine can show the presence of chemicals characteristic of the disorder. In older children and adults, doctors will look for symptoms of CTX, including:

  • Chronic diarrhea
  • Cataracts at an early age
  • Fatty tumors in the tendons
  • High cholesterol levels in the tendons but normal or low cholesterol in the bloodstream

Other diagnostic steps may include:

  • Imaging scans such as magnetic resonance imaging (MRI) to look for abnormalities in the brain
  • Genetic testing to look for CYP27A1 mutations


How Is Cerebrotendinous Xanthomatosis Treated?

CTX has no cure, but treatment is often effective at slowing, stopping, or sometimes reversing the disorder’s progression. Common treatments and therapies include:

  • Chenodeoxycholic acid (CDCA) replacement therapy to limit cholesterol accumulation and improve symptoms
  • HMG-CoA reductase inhibitors to reduce cholesterol production
  • Cholic acid treatment in patients who can’t tolerate CDCA
  • Cataract surgery

How Does Cerebrotendinous Xanthomatosis Progress?

When treated early, CTX is usually a manageable condition. People who receive the proper treatment early on may not develop serious complications, and their life expectancy is in the normal range. However, when the condition is left untreated, life-limiting and potentially fatal complications are likely to develop.

Potential long-term complications of  CTX include:

  • Seizures
  • Movement problems
  • Speech impairment
  • Loss of feeling in the arms and legs
  • Vision impairment
  • Brittle bones
  • Heart disease
  • Lung disease
  • Intellectual impairment
  • Dementia
  • Hallucinations
  • Depression
  • Suicide attempts

How Is Cerebrotendinous Xanthomatosis Prevented?

There is no known way to prevent CTX when the disorder-causing gene mutations are present. However, the most severe complications of the condition may be prevented with early diagnosis and prompt treatment.

Parents with a family history of the disorder or who have had another child with CTX are advised to consult a genetic counselor to assess their risk if they plan to have another child.

Cerebrotendinous Xanthomatosis Caregiver Tips

  • Be watchful for the signs of CTX. This disorder is rare and may escape the notice of even medical professionals, but early diagnosis and treatment are vital. Be aware of the symptoms of CTX, and tell your doctor if you see them in your child.
  • Learn about CTX, and find a community. The United Leukodystrophy Foundation has gathered a collection of resources to help you, along with other families like you, find information about the disorder.

Some people with CTX also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with CTX:

Cerebrotendinous Xanthomatosis Brain Science

The CYP27A1 gene carries instructions for making an enzyme called sterol 27-hydroxylase. This enzyme plays a role in a process in which cholesterol is broken down into a bile acid called chenodeoxycholic acid. However, CYP27A1 mutations interfere with the production of sterol 27-hydroxylase. As a result, chenodeoxycholic acid production is inhibited, and other chemicals, such as bile alcohols and a fatty substance called cholestanol, are produced instead.

Cholesterol and cholestanol accumulate in various places in the body, including the eyes, heart, tendons, and brain. In some areas, these fatty substances form benign tumors called xanthomas. In the brain, xanthomas and fats interfere with myelin, a substance that coats nerve cells and helps them function. As myelin breaks down, the nerve cells are unable to communicate with one another and gradually deteriorate – the neurological symptoms of CTX result.

Cerebrotendinous Xanthomatosis Research

Title: Phase II Study of Cholesterol- and Cholestanol-Free Diet, Lovastatin, and Chenodeoxycholic Acid for Cerebrotendinous Xanthomatosis

Stage: Recruiting

Study chair: William Connor

Oregon Health and Science University

Portland, OR


I. Assess the biosynthesis of cholesterol and cholestanol and measure the turnover of individual sterols and bile acids in patients with cerebrotendinous xanthomatosis before and after cholesterol and cholestanol-free diets.

II. Assess the biosynthesis of cholesterol and cholestanol and measure the turnover of individual sterols and bile acids in these patients before and after lovastatin and chenodeoxycholic acid.

PROTOCOL OUTLINE: Following a 2-week baseline assessment, patients participate in a feeding study for up to 3 weeks. The diet is free of cholesterol and cholestanol.

For the next four weeks, patients return to their typical diet and medicate with daily lovastatin and chenodeoxycholic acid.

The feeding study is repeated for an additional three weeks, with the patient taking either lovastatin or chenodeoxycholic acid.


Title: The Prevalence of CTX Disorder in Juvenile Cataract Cases in Turkey (GEN-EYE-I)

Stage: Recruiting

Contact: Aysel Pelit

Adana Başkent University School of Medicine

Adana, Turkey

This epidemiologic observational study will include two phases:

Retrospective cross-sectional phase: At this stage of the study, retrospective screenings are carried out at study sites, and all juvenile cataract cases are planned to be determined.

Prospective phase: At this stage of the study, identified juvenile cataract cases resulting from retrospective screenings will be called and be invited to the sites. Blood samples will be obtained for the cholestanol tests for the cases that have given Informed Consent.

This observational study is designed in two phases; retrospective and prospective. The retrospective part includes screening the patient database and/or patient files at ophthalmology clinics participating in the study and identifying patients diagnosed with idiopathic juvenile cataracts. The data of patients with idiopathic juvenile cataracts will be reviewed, and the data of the patients meeting the inclusion/exclusion criteria will be recorded. Once this phase is completed, the prospective phase of the study will start, and the patients meeting the criteria will be invited to the site to participate in the study. Current data will be collected from the patients who agree to participate in the study, and the clinical status of the patients will be evaluated according to the Mignarri index. In addition, blood will be obtained from all patients to diagnose CTX disease. Blood samples will be sent to Duzen Laboratories in Ankara and analyzed for cholestanol.

You Are Not Alone

For you or a loved one to be diagnosed with a brain or mental health-related illness or disorder is overwhelming, and leads to a quest for support and answers to important questions. UBA has built a safe, caring and compassionate community for you to share your journey, connect with others in similar situations, learn about breakthroughs, and to simply find comfort.

United Brain Association

Make a Donation, Make a Difference

We have a close relationship with researchers working on an array of brain and mental health-related issues and disorders.  We keep abreast with cutting-edge research projects and fund those with the greatest insight and promise.  Please donate generously today; help make a difference for your loved ones, now and in their future.                                                                 

The United Brain Association – No Mind Left Behind

Share Your Story

If you have an experience, a story, or someone in your life you want to recognize for their strength and willpower, please share it with us. We want to hear from you because listening is part of healing.

Connect With Us

Receive news on Brain Awareness, the Latest Research, and Personal Stories