Cerebrotendinous xanthomatosis – genetic testing for CTX

Cerebrotendinous xanthomatosis (CTX) is a rare genetic storage disorder. This disorder’s name derives from accumulations of cholesterol in the brain and tendons, these accumulations appear as yellow fatty tumors (nodules) known as xanthomas. CTX has a prevalence of 2 in 100,000 births, it is more frequent among Caucasian population.


The genetic basis of CTX

CTX is a genetic disorder caused by a mutation in the CYP27A1 gene. This gene encodes a protein that breaks down cholesterol. Mutations to this gene cause an abnormal accumulation of cholesterol in various body tissues.

This abnormal accumulation is toxic to the cells, and especially harmful to brain cells. This disease has an autosomal recessive inheritance pattern which means that two mutated gene copies (one from each parent) must be inherited to develop the disorder. Gene mutation carriers can pass one mutated copy of the mutation to their children. If both parents are carriers, their child can inherit two mutated gene copies and therefore develop the disorder.


Signs and symptoms

The most common signs of this genetic disorder include various neurological and developmental impairments, including intellectual disability, dementia, epilepsy, symptoms that resemble Parkinson’s disease, and peripheral neuropathy. 

Neurological signs first appear during late childhood and occasionally in young adults. Unfortunately, this disease is progressive, and symptoms worsen with age.

Non-neurological symptoms include chronic diarrhea that does not respond to medication, cataracts at a young age, xanthomas (cholesterol accumulations on the tendons), atherosclerosis, and heart disease.

All symptoms are linked to excess cholesterol in the tissues: excess cholesterol in the lens of the eye leads to cataracts, cholesterol accumulations in the tendons cause xanthomas, and cholesterol accumulations in the blood vessels lead to atherosclerosis, heart attacks, and strokes at a young age.


How is CTX diagnosed?

Brain imaging tests show an atrophy of brain tissue, resulting from the damage caused to the cells by cholesterol. Changes in specific areas of the brain have unique patterns that can be identified by specialists. Patient’s blood tests show cholesterol levels that are up to ten times higher than normal.

Several symptoms that appear at a young age can raise suspicion for CTX, these include chronic diarrhea, obstructive jaundice in newborns, cataracts during infancy, and cognitive decline. When these signs are added to high cholesterol levels, genetic testing can be used to diagnose the disease. Families are referred to genetic counselling and can choose methods such as PGD and IVF to ensure the health of their children in subsequent pregnancies. 



There is no cure for CTX. However, a bile acid known as Chenodeoxycholic acid can be used to delay the disease’s progression but does not improve patients’ cognitive condition. CTX is characterized by low levels of this bile acid. There is no evidence that conventional therapy against high levels of cholesterol (such as statins) is effective for treating CTX.


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