Cerebrotendinous xanthomatosis

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Cerebrotendinous xanthomatosis (CTX) is a rare genetic neurometabolic disorder of bile acid synthesis, resulting in abnormal accumulation of cholestanol and other sterols in multiple tissues. It occurs as an inherited autosomal recessive genetic condition; absence of a relevant family history does not exclude the diagnosis because the parents of an affected individual are typically unaffected carriers. A distinctive presentation may include the combination of Achilles tendon xanthomas, progressive neuropsychiatric manifestations, chronic diarrhea, and juvenile cataracts.

It can present with psychiatric features such as behavioural or personality change, depression, anxiety, irritability, agitation, aggression, and psychosis. Psychiatric manifestations may become apparent or clinically significant during adolescence or adulthood and may precede or accompany the characteristic neurologic manifestations. Schizophrenia-like presentations with delusions and hallucinations have been reported.

Other characteristic features include progressive cognitive impairment or dementia, ataxia, spasticity or spastic paraparesis, dystonia, parkinsonism, peripheral neuropathy, seizures, dysarthria, and other progressive neurologic manifestations. Juvenile or early-adult cataracts and tendon xanthomas, particularly involving the Achilles tendons, are highly characteristic.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Cardiovascular: premature atherosclerosis and coronary artery disease may occur.

  • Gastrointestinal: chronic diarrhea is a characteristic early manifestation and may begin in infancy; gallstones may also occur.

  • Hepatobiliary: neonatal cholestasis or jaundice and, less commonly, hepatic involvement may occur.

  • Musculoskeletal: tendon xanthomas, particularly of the Achilles, patellar, hand, elbow, and neck tendons, as well as osteopenia or osteoporosis, may occur.

Early diagnosis is important to recognize a potentially treatable cause of psychiatric and progressive neurologic illness; prevent or slow potentially irreversible neurologic deterioration; reduce the risk of osteoporosis, fractures, cardiovascular complications, and other systemic disease; initiate chenodeoxycholic acid treatment promptly; and enable appropriate genetic counselling and screening of at-risk relatives.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.