Cerebrotendinous xanthomatosis




Cerebrotendinous xanthomatosis is a fat (lipid) storage disorder that affects many areas of the body. People with this disorder cannot break down certain lipids effectively, specifically different forms of cholesterol, so these fats accumulate in various areas of the body. Xanthomatosis refers to the formation of fatty yellow nodules (xanthomas). Cerebrotendinous refers to the typical locations of the xanthomas (cerebro- meaning the brain and -tendinous meaning connective tissue called tendons that attach muscle to bone).

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. 

Other features of cerebrotendinous xanthomatosis include chronic diarrhea during infancy, clouding of the lens of the eye (cataracts) developing in late childhood, progressively brittle bones that are prone to fracture, and neurological problems in adulthood, such as dementia, seizures, hallucinations, depression, and difficulty with coordinating movements (ataxia) and speech (dysarthria). The neurological symptoms are thought to be caused by an accumulation of fats and an increasing number of xanthomas in the brain. Xanthomas can also accumulate in the fatty substance that insulates and protects nerves (myelin), disrupting nerve signaling in the brain. Disorders that involve the destruction of myelin are known as leukodystrophies. Degeneration (atrophy) of brain tissue caused by excess lipid deposits also contributes to the neurological problems.

Xanthomas in the tendons (most commonly in the Achilles tendon, which connects the heel of the foot to the calf muscles) begin to form in early adulthood. Tendon xanthomas may cause discomfort and interfere with tendon flexibility. People with cerebrotendinous xanthomatosis are also at an increased risk of developing cardiovascular disease. If untreated, the signs and symptoms related to the accumulation of lipids throughout the body worsen over time; however, the course of this condition varies greatly among those who are affected.


The symptoms associated cerebrotendinous xanthomatosis are listed below, including the typical age when each symptom appears.

  • Chronic diarrhea (infancy)
  • Cataracts (early childhood)
  • Mental impairment (infancy or at puberty)
  • Xanthomas (adolescents to early adulthood)
  • Dementia with slow deterioration in intellectual abilities (early adulthood)
  • Progressive neurologic dysfunction
  • Spasticity (early adulthood)
  • Cerebellar signs such as intention tremor, difficulty with fast hand movements, nystagmus, truncal ataxia, and rhomberg's sign) (early adulthood)
  • Behavioral changes (early adulthood)
  • Hallucinations (early adulthood)
  • Agitation (early adulthood)
  • Aggression (early adulthood)
  • Depression (early adulthood)
  • Suicide attempt (early adulthood)
  • Other symptoms may include dystonia, atypical parkinsonism, seizures, and peripheral neuropathy
  • Cerebellopyramidal signs, myoclonus of the soft palate, mental debility, xanthelasmata,
  • Progressive ataxia.
  • Progressive frontal lobe dementia and spastic paraplegia


Mutations in the CYP27A1 gene cause cerebrotendinous xanthomatosis. The CYP27A1 gene provides instructions for producing an enzyme called sterol 27-hydroxylase. This enzyme works in the pathway that breaks down cholesterol to form acids used in the digestion of fats (bile acids). Mutations in sterol 27-hydroxylase impair its ability to break down cholesterol to a specific bile acid called chenodeoxycholic acid. As a result, a molecule called cholestanol, which is similar to cholesterol, accumulates in xanthomas, blood, nerve cells, and the brain. Cholesterol levels are not increased in the blood, but they are elevated in various tissues throughout the body. The accumulation of cholesterol and cholestanol in the brain, tendons, and other tissues causes the signs and symptoms of cerebrotendinous xanthomatosis.


Signs and symptoms of Xanthomatosis cerebrotendinous may vary on an individual basis for each patient. Also, testing of the CYP27A1 gene is available.


Cerebrotendinous xanthomatosis may be treated with chenodeoxycholic acid (CDCA), which has been shown to normalize levels of cholestonal and improve neurologic symptoms. Inhibitors of HMG-CoA reductase may be used alone or in combination with CDCA. They are also effective in decreasing cholestanol concentration and improving clinical symptoms, however these treatments can induce muscle damage. Coenzyme Q10 may improve muscle weakness, and cataract surgery may also be required.


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