More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Also known as: Cerebral Cholesterinosis; Sterol-27-hydroxylase deficiency
Cerebrotendinous Xanthomatosis (CTX) is a rare genetic disorder caused by mutations in the CYP27A1 gene. It leads to a deficiency in the enzyme responsible for bile acid synthesis, resulting in the buildup of cholesterol and cholestanol in various tissues, particularly the brain and tendons. This commonly leads to tendon xanthomas (yellow, cholesterol deposits), cataracts, and diarrhoea. If untreated, it can lead to progressive neurological problems such as seizures, behavioural changes, and difficulties with coordination and balance. Early diagnosis and treatment with bile acid replacement therapy are crucial to slow disease progression and improve quality of life.
A new diagnosis can be overwhelming as it brings unique challenges and adjustments, but it is important to remember that you are not alone.
CTX is caused by mutations in the CYP27 gene resulting in deficient activity of chemical sterol-27-hydroxylas which is important in initiating the Bile Acid Synthesis (BAS) pathway. This means that bile acid synthesis is disrupted, creating a build up of cholesterol and cholestenol causing the degenerative problems described.
Autosomal recessive: In autosomal recessive conditions, two copies of the genetic mutation are needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. The parents of someone with an autosomal recessive condition both carry one copy of the gene with a genetic mutation. Therefore, someone with an autosomal recessive condition has two copies of the genetic mutation, one copy from each parent. Each child of parents that both carry the genetic mutation will have a 25% chance of having the condition, a 50% chance of carrying the genetic mutation (like the parent), and a 25% chance of not having the condition.
Genetic counselling is essential for affected families due to the inheritance pattern of the condition. This is available at hospitals and Regional Genetic Centres. Please contact your doctor if you have any questions.
Learn more about genetic testing and counselling here.
A common first sign of CTX is neonatal cholestastatic (reduction or stoppage of bile flow) jaundice , shown as yellowing of the skin and whites of the eyes, itchy skin, dark urine and light-coloured, foul-smelling stools. Chronic diarrhoea and liver dysfunction may also occur. Children with CTX often suffer from cataracts. Xanthomas (yellowish, cholesterol-rich deposits showing abnormal storage of fats and occurring anywhere on the body,) are common on the elbow, hand, patella, neck and Achilles tendon.
While some intellectual impairment may be noticed in childhood, this is more common from puberty onwards. Dementia, psychiatric disturbances and nerve damage progress with age, with dementia often happening in a person’s 20’s alongside behavioural changes. These changes may include hallucinations, aggression, depression and suicidal tendencies.
Life expectancy without treatment is around 50-60 years, though there have been reports of some passing away during infancy.
Learn more about specific symptoms of this leukodystrophy in these pages.
Treatment of CTX is possible through CDCA (chenodeoxycholic acid) replacement therapy, which can halt and even reverse symptoms. Cholic acid treatment is another alternative treatment.
Patients in the UK should refer to the NHS Clinical Commissioning Policy: Cholic acid and chenodeoxycholic acid for treating inborn errors of bile acid synthesis (all ages)
There is also condition management information that may be useful for you in managing your or your loved one’s leukodystrophy.
There may be a current clinical trial, natural history study or patient registry for your condition. Check our current research page and ask your specialist doctor for more information.
We understand that research is a significant priority and source of hope for the leukodystrophy community. There is more research in leukodystrophy now than ever before. Alex TLC actively promotes and supports research in a number of ways.
Every month we update our database of research summaries with the most recent research. This includes summaries of leukodystrophy articles, clinical trials and pharmaceutical press releases. Our summaries allow our community to read about relevant recent research developments in a format that is easily understood.
Learn about the ways in which we can help in the how we support you section. When you or a family member been diagnosed with a leukodystrophy it may be difficult to know where to go for more advice – this information could help.
Our services and equipment section is here to help leukodystrophy patients and their families manage their condition. All information is based on our knowledge of UK services, however, our team are happy to receive support requests from other countries – email us.
You may be introduced to many different medical professionals which you may find confusing. View our guide to the health and care professionals you may encounter, with short descriptions about what they do.
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