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HomeHealth articlesgenetic mutationWhat Is Cerebrotendinous Xanthomatosis?

Cerebrotendinous Xanthomatosis- Causes, Symptoms, Diagnosis, and Management

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Cerebrotendinous xanthomatosis is a condition affecting the fat metabolism of the body. This article reviews cerebrotendinous xanthomatosis and its management.

Medically reviewed by

Dr. Prakashkumar P Bhatt

Published At December 29, 2022
Reviewed AtDecember 29, 2022


Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disorder affecting the fat metabolism of the body. In cerebrotendinous xanthoma, the body is unable to break down the fat cells (cholesterol), so they accumulate in some areas of the body. It is an autosomal recessive disorder that causes abnormality in the CYP27A1 gene. This gene mutation causes a deficiency of the enzyme 27- hydroxylase, which is responsible for the breakdown of fats into bile acids. So these fatty cells get deposited in the body tissues and appear as yellow nodules. In these patients, the blood cholesterol levels appear normal, but they are seen as elevated levels in the tissues.

When Was Cerebrotendinous Xanthomatosis (CTX) Discovered?

Cerebrotendinous xanthoma (CTX) was first described in the scientific literature in the year 1937. It was categorized as a bile acid synthesis disorder due to the deficiency of the enzyme 27- hydroxylase, which is essential for bile acid synthesis. Later, it was classified as a lipid storage disease due to the deposition of the fats seen in the body parts.

What Are the Other Names for Cerebrotendinous Xanthomatosis?

  • Cerebral cholesterolosis.

  • Cerebrotendinous cholesterolosis.

  • Cholesterolosis.

  • Cholestanol storage disorder.

  • Van Bogaert-Scherer-Epstein disease.

What Are Autosomal Recessive Conditions and CYP27A1 Genes?

In autosomal recessive conditions, there should be two copies of mutated or abnormal genes to cause the genetic defect. If both the parents carry one mutated gene each, then they are referred to as carriers of the disease. Here, they are not affected by the disease, but they can pass it on to their children. In these cases, the child has a one in four chance of presenting with the disease.

CYP27A1: The cytochrome P27A1 is a gene that provides instructions to the body to produce the enzyme sterol 27- hydroxylase. This enzyme 27-hydroxylase is present in the energy-producing cells of the body, ‘the mitochondria.’ The enzyme is responsible for breaking down the complex cholesterol molecules into bile acids that digest the fat cells.

How Common Is This Condition?

  • Cerebrotendinous xanthomatosis is a rare medical condition that affects only one in 10,00,000 people.

  • They are seen more in the Moroccan-Jewish population, with an incidence of one in 108 people.

  • It affects males and females equally in a ratio of 1:1.

  • They are commonly seen during the second and third decades of life (10 to 20 years).

What Causes Cerebrotendinous Xanthomatosis?

CTX is caused due to the mutation of the gene CYP27A1, which is essential and instructs the body to create proteins for several body functions. This gene mutation results in the deficiency of sterol 27-hydroxylase, which is a mitochondrial enzyme. This deficiency prevents the conversion of cholesterol to chenodeoxycholic acid, which is a bile acid. This bile acid is responsible for digesting the fat cells. So there is an accumulation of the intermediate products (cholestanol) in the blood and tissues resulting in elevated levels of cholesterol in the blood, but the blood cholesterol levels appear normal.

Causes Cerebrotendinous Xanthomatosis

What Are the Symptoms of Cerebrotendinous Xanthomatosis?

The symptoms vary in each individual, and it depends on the severity of the condition. The symptoms are categorized based on the age of the affected individual.

Symptoms Seen During Childhood:

  • Failure to thrive.

  • Persistent diarrhea.

  • Cognitive impairment.

  • Cataracts (the eye lenses become cloudy, interfering with eyesight) are commonly seen either in one or both eyes.

  • Brittle bones are highly susceptible to fractures.

  • Hepatomegaly and splenomegaly (enlargement of spleen and liver)

Symptoms Seen During Adulthood:

  • Memory loss or dementia.

  • Seizures are commonly encountered.

  • Disturbances in mental health with increased agitation, depression, and hallucinations. Suicide attempts are also seen in these patients.

  • Stroke and cardiac attacks are due to the deposition of fatty substances along the blood vessel wall.

How to Diagnose This Disease?

The clinician makes the diagnosis from the physical examination and from a thorough medical history. However, to confirm the diagnosis, the presence of any two of the following criteria is required:

  • Persistent diarrhea.

  • Development of cataracts during childhood.

  • Neurological defects.

  • Fatty deposition of cholesterol in the tendons.

What Are the Diagnostic Procedures?

  • Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) Scans: These tests detect any abnormalities inside the brain and the blood vessels. This can rule out stroke and any other neurological damage to the tissues.

  • Angiography: The cerebrovascular examination of the blood vessels of the brain is done by angiography. Angiography is a type of X-ray that detects abnormalities in the blood vessels. Here, the blood vessels are examined for fatty deposition and its severity.

  • Echocardiography: The heart valves and the blood vessels of the heart are assessed. The echocardiogram uses sound waves to capture the functioning of the heart and its muscles.

  • Molecular Genetic Testing: The genetic test detects the presence of any abnormalities in the genes. This molecular genetic testing helps to rule out the variations in the CYP27A1 gene that is responsible for cerebrotendinous xanthoma.

How to Manage Cerebrotendinous Xanthomatosis?

Cerebrotendinous xanthomatosis is a genetic condition, and there is no permanent cure for this disease. However, early diagnosis can help to prevent the progression of this condition. Palliative treatment is given to provide symptomatic relief and to improve the quality of life.

  • Chenodeoxycholic Acid Replacement Therapy (CDCA): It is the first line of treatment, and it focuses on the breakdown of cholesterol. So chenodeoxycholic acid therapy should be started immediately. These medications help in enhancing the body’s ability to break down cholesterol and normalize the cholestanol levels in the body. Cholic acid is also given to reduce cholesterol levels.

  • HMG-CoA Reductase Inhibitors: They help to lower the cholesterol levels in the body by blocking the enzymes responsible for cholesterol synthesis.

  • Surgeries: Cataract surgeries are recommended after the age of 50 to provide symptomatic relief in the patient and to improve eyesight.


Although there is no cure and definitive treatment for cerebrotendinous xanthomatosis, symptomatic treatment is done that provides relief and improves the quality of the affected individuals. Early detection of cerebrotendinous xanthomatosis helps in preventing the progression and slowing down of the condition. If left untreated, the symptoms may worsen. If there is any known family history, then genetic testing can be done to test for the presence of the defect in children during the prenatal stage itself. Proper genetic counseling should be given to the parents and other family members. Chenodeoxycholic acid therapy should never be interrupted during pregnancy.

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Dr. Prakashkumar P Bhatt
Dr. Prakashkumar P Bhatt



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