Cerebrotendinous Xanthomatosis

By | June 10, 2022

Cerebrotendinous xanthomatosis is a very rare metabolic disease that is usually inherited in an autosomal recessive manner. In some cases, the disease is simply referred to by the abbreviation CTX. Cerebrotendinous xanthomatosis belongs to the category of so-called leukodystrophies. The disease was first described by Epstein, van Bogaert and Scherer in 1937. For this reason, the disease is sometimes also called Van Bogaert-Scherer-Epstein syndrome.

What is cerebrotendinous xanthomatosis?

Cerebrotendinous xanthomatosis is a rare lipid storage disease. In the disease there is an abnormality in the formation of bile acids. For this reason, cerebrotendinous xanthomatosis is in most cases associated with, for example, neonatal cholestasis and cataracts that develop in childhood. For meanings of lagophthalmos, please visit polyhobbies.com.

Adolescents and young adults develop tendinous xanthoma or xanthoma in the brain as part of the disease. In adulthood, disorders of the neurological functions set in. More than 300 cases of cerebrotendinous xanthomatosis have been described worldwide.

In people from Europe, the frequency is estimated at about 1:50,000. Since the disease is inherited in an autosomal recessive manner, genetic counseling is recommended in the relevant families.


There are many potential causes for the development of cerebrotendinous xanthomatosis. Basically, it is a metabolic disease characterized by a deficiency in the enzyme sterol-27-hydroxylase. This special enzyme plays an essential role in the formation of bile acids.

Due to the deficiency, the substance 5β-cholestane-3α, 7α, 12α-triol accumulates in the liver. A hydroxylase of the substance to bile alcohols takes place. In addition, cholestanol, which is a hydrogenated type of cholesterol, is formed. The substance accumulates in numerous types of tissue, particularly in the nervous system.

In principle, cerebrotendinous xanthomatosis is caused by a mutation in the sterol-27-hydroxylase gene. Inheritance is autosomal recessive. This gene is essential for bile metabolism, which is why errors in the gene lead to functional disorders.

As a result, metabolic products of bile acid synthesis accumulate in the tissue and plasma of the organism. In addition, bile alcohols are increasingly excreted in the urine. In addition, the substances cholestanol and cholesterol are deposited in connection with degenerative processes.

Symptoms, Ailments & Signs

In the context of cerebrotendinous xanthomatosis, numerous different symptoms and complaints appear in the affected patients. The signs of the disease vary individually depending on the individual case, severity and degree of severity. The first clinical symptom is usually cholestasis or chronic diarrhea, which already occurs in infants.

In addition, a cataract sometimes forms. In many cases, other symptoms only appear between the ages of 20 and 40. This often leads to neurological abnormalities, which are associated, for example, with motor dysfunctions. Various types of behavioral problems as well as dementia and ataxia are also possible.

Xanthomas sometimes form in the area of ​​the Achilles tendon, although other tendons can also be affected, for example on the hands or elbows. These xanthomas form because plasma lipoproteins are increasingly stored. Some patients in infancy also show a disturbance of the liver function.

Some of the people affected show intellectual limitations as early as childhood. However, in the majority of cases, intelligence is normal or slightly below average up until puberty. However, neurological dysfunctions are becoming increasingly evident in adulthood. Psychiatric abnormalities, neuropathy or seizures are possible.

Dementia develops in more than half of the affected patients between the ages of 20 and 30. There are also various neuropsychiatric symptoms, such as hallucinations, aggression and depression, including suicidal tendencies. So-called pyramidal signs or cerebellar ataxia form. Peripheral neuropathy also occurs in some cases.

Diagnosis & course of disease

With regard to the diagnosis of cerebrotendinous xanthomatosis, there are various examination measures to choose from. The attending physician weighs their use after considering the individual case. Since bile alcohols are excreted via the kidneys as glucuronides, laboratory detection in the urine is possible. The cholestanol can be detected in the plasma.

An elevated level of cholestanol in the plasma is decisive for the diagnosis. The concentration is five to ten times higher than normal. However, the diagnosis of cerebrotendinous xanthomatosis can only be made with certainty when a CYP27A1 mutation has been determined by molecular genetics.

In infants and small children, the urinalysis already gives important indications of a possible cerebrotendinous xanthomatosis. Other reasons for the development of xanthomas, such as hyperlipidemia or sitosterolemia, must be clarified as part of the differential diagnosis . In addition, a prenatal diagnosis via the embryonic tissue is also possible.


If left untreated, cerebrotendinous xanthomatosis progresses inexorably. The life expectancy of the patients in these cases is between 50 and 60 years. The earlier the therapy begins, the better the prognosis of the disease and the less often complicated courses occur. The first symptoms already appear in infancy.

This leads to chronic diarrhea and possible liver dysfunction and cholestasis. Deaths in newborns are also possible due to this. A few patients show mental limitations as early as infancy, while the majority of those affected have normal intelligence up to puberty. Furthermore, a cataract is already found in about 75 percent of newborns.

Early therapy can stop the progression of the disease and sometimes even reverse it. Otherwise, in adulthood, there will be an increasing number of neurological disorders, which manifest themselves in the form of psychiatric abnormalities, dementia, seizures, neuropathies and pyramidal signs. More than half of the patients develop dementia in their twenties.

In addition, some sufferers experience hallucinations, depression, suicidal thoughts, and altered behavior. In addition, there are pathological reflexes (pyramidal sign), disturbances in the coordination of movements as well as tingling and numbness in the hands and feet. The severity of the disease varies between patients. Without treatment, however, these degenerative processes will inevitably intensify through further deposits of cholesterol and cholestanol.

When should you go to the doctor?

If a member of the family has been diagnosed with cerebrotendinous xanthomatosis, a doctor should always be consulted before planning a child. It is advisable to clarify possible risks and to adequately weigh up all available options. In most cases, the first symptoms appear between the ages of 20 and 40. Therefore, people who suffer from health changes and abnormalities in particular should consult a doctor. Nevertheless, the first irregularities are already evident in infants.

These are often so diffuse that no adequate diagnosis can be made. Persistent diarrhea is a cause for concern. The person concerned should consult a doctor and insist on an intensive check-up. Changes in behavior and irregularities in mobility must be examined and treated. A doctor should be consulted in the event of a loss of the usual cognitive performance and particularly in the case of memory disorders.

Changes in the complexion, seizures or emotional peculiarities are also part of the symptoms of the disease. A doctor’s visit is necessary for a diagnosis to be made. If hallucinations, depressive states or signs of suicidal tendencies appear, immediate action must be taken. In the event of disturbances in the general movement sequences and in the coordination of locomotion, the observations should be discussed with a doctor.

Treatment & Therapy

The administration of chenodeoxycholic acid is an option for the therapy of cerebrotendinous xanthomatosis, since the affected persons completely lack it. Taking this acid normalizes the concentration of cholestanol. Administration of HMG-CoA reductase inhibitors is also possible. Adequate therapy usually improves the neurological symptoms significantly.


Effective measures for the prevention of cerebrotendinous xanthomatosis are not yet known, since the disease is mainly based on genetic causes.


Cerebrotendinous xanthomatosis is mainly genetic, so there are few effective follow-up and preventive measures. Following the drug therapy, the state of health of those affected gradually returns to normal. However, the different symptoms still require close observation.

If patients and their relatives notice any irregularities during the follow-up phase, they should immediately seek medical advice. Those affected often suffer from restricted mobility, which has an impact on everyday processes. Therefore, as the disease progresses, they often need special aids such as walkers, wheelchairs or stair lifts.

Depending on the severity of the pain caused by the disease, patients can take medication to relieve it. You should always discuss this with your doctor to find out about the appropriate active ingredients. The quality of life for those affected is reduced as the condition progresses, which is why the treating doctor often advises participation in a self-help group.

Here the patients learn to deal better with their fate. Especially when dealing with this chronic disease, the psyche also suffers. Those affected can obtain information about this form of aftercare from their health insurance company or from the social organizations in their town.

You can do that yourself

Everyday life with cerebrotendinous xanthomatosis is often difficult to cope with on your own due to the wide range of symptoms. Support from family members or trained professionals is the best way to support those affected. Limited mobility prevents a normal daily routine. In the case of an advanced clinical picture and complete immobility, devices such as stair lifts or wheelchairs make everyday life easier.

To relieve pain, an additional intake of over-the-counter painkillers can help. Drugs with the active ingredients ibuprofen or paracetamol are suitable for pain therapy. Painkillers should not be taken without prior consultation with the treating specialist.

In order to better process one’s own fate with cerebrotendinous xanthomatosis, it can be helpful to exchange ideas with other sufferers. Self-help groups for rare and chronic diseases are a good place to go for those who are ill. Information about groups and dates can be found at social organizations and health insurance companies.

Apart from conventional medical treatment of the disease, there is no effective alternative treatment method. Supportive medicines from naturopathy show no effect on the sick. Likewise, no preventive measures are known to prevent disease with cerebrotendinous xanthomatosis. Those affected can obtain further information about supportive measures from their health insurance companies and general practitioners.

Cerebrotendinous Xanthomatosis