Cerebrotendinous xanthomatosis: Molecular pathogenesis, clinical spectrum, diagnosis, and disease-modifying treatments

The Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare of Japan

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder caused by mutations in the CYP27A1 gene, which encodes the mitochondrial enzyme sterol 27-hydroxylase. Decreased sterol 27-hydroxylase activity results in impaired bile acid synthesis, leading to reduced production of bile acids, especially chenodeoxycholic acid (CDCA), as well as elevated serum cholestanol and urine bile alcohols. The accumulation of cholestanol and cholesterol mainly in the brain, lenses, and tendons results in the characteristic clinical manifestations of CTX. Clinical presentation is characterized by systemic symptoms including neonatal jaundice or cholestasis, refractory diarrhea, juvenile cataracts, tendon xanthomas, osteoporosis, coronary heart disease, and a broad range of neuropsychiatric manifestations. The combinations of symptoms vary from patient to patient and the presenting symptoms, especially in the early disease phase, may be nonspecific, which leads to a substantial diagnostic delay or underdiagnosis. Replacement of CDCA has been approved as a first-line treatment for CTX, and can lead to biochemical and clinical improvements. However, the effect of CDCA treatment is limited once significant neuropsychiatric manifestations are established. The age at diagnosis and initiation of CDCA treatment correlate with the prognosis of patients with CTX. Therefore, early diagnosis and subsequent treatment initiation are essential.

Original languageEnglish
Pages (from-to)905-925
Number of pages21
JournalJournal of atherosclerosis and thrombosis
Issue number9
Publication statusPublished - 2021


  • CTX
  • CYP27A1
  • Cerebrotendinous xanthomatosis
  • Chenodeoxycholic acid
  • Cholestanol

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical


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