What is Cerebrotendinous Xanthomatosis?
Cerebrotendinous Xanthomatosis (CTX) is an inherited disorder in which affected individuals do not make bile acids normally. Affected individuals are unable to make normal amounts of a bile acid, chenodeoxycholic acid (CDCA), and therefore chemicals that are supposed to be converted to CDCA accumulate in various parts of the body. CTX is characterized by childhood diarrhea, cataracts and tendon xanthomas, which are soft bumps under the skin made up of yellow fatty deposits. As children grow older, they may lose mental capability and begin to show signs of abnormal movements and balance. The symptoms of CTX can vary widely between affected individuals.
Common symptoms include:
- Tendon xanthomas
- Progressive abnormal movements and balance problems
- Cholesterol deposits in the brain
- Intellectual disability
- Chronic diarrhea
- Prolonged jaundice as a baby
- Psychiatric symptoms
- Degeneration of parts of the brain
- Premature atherosclerosis
How many people have Cerebrotendinous Xanthomatosis?
CTX is estimated to occur in 1 in 50,000 individuals worldwide and is more commonly seen in the Moroccan Jewish population with an incidence of 1 in 108 individuals in that group, as well as being more common in the Druze.
What causes Cerebrotendinous Xanthomatosis?
CTX is caused by a mutation or change in the CYP27A1 gene, (CYP27A1), which makes the enzyme sterol 27-hydroxylase. This enzyme helps in the formation of bile acids, which are important for fat absorption in our bodies, from cholesterol. Mutations or changes in the CYP27A1 gene cause accumulation or storage of cholesterol-like substances in the blood, nerve cells, and the brain.
CTX is an inherited autosomal recessive disorder. Affected individuals inherit two copies of the mutated or changed gene, one from each parent. Therefore the parents are "carriers" of CTX, meaning that they have one normal functioning copy and one nonfunctioning copy of the CYP27A1 gene. With each pregnancy, carriers of CTX have a 1 in 4 or 25% chance of having a child with CTX.
How is Cerebrotendinous Xanthomatosis diagnosed?
CTX is diagnosed based on clinical features and blood testing. Abnormalities seen in the blood in individuals with CTX include high levels of cholestanol (a cholesterol-like metabolite), decreased chenodeoxycholic acid, and increased concentrations of certain bile alcohols. Genetic testing for the gene associated with CTX, CYP27A1 is also available to confirm the diagnosis and allow carrier and prenatal testing.
What is/Is there treatment for Cerebrotendinous Xanthomatosis?
Oral CDCA replacement therapy, available in the US as Chenodal, has been shown to be an effective treatment and is prescribed off-label. Cholic acid may also be effective in CTX, but there is much less experience using this medication.
OMIM.org: Cerebrotendinous Xanthomatosis