Pathophysiology and Treatment of Lipid Abnormalities in Cerebrotendinous Xanthomatosis: An Integrative Review

Abstract

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons and peripheral nerves. We conducted this review to evaluate lipid profile abnormalities in patients with CTX. A search was conducted in PubMed, Embase and the Virtual Health Library in January 2023 to evaluate studies reporting the lipid profiles of CTX patients, including the levels of cholestanol, cholesterol and other lipids. Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.

Keywords: cerebrotendinous xanthomatosis; chenodeoxycholic acid; cholestanol; cholesterol; lipid.

Figure 1

Cholesterol metabolism and changes in cholesterol metabolism present in patients with CTX. Adapted and modified with permission from [3].

Figure 2

Neuroimaging patterns observed in CTX. Axial brain MRI disclosed signal change in deep cerebellar white matter and dentate nucleus (white arrows) which were hypointense on T1W (A) and hyperintense in T2W (B) and FLAIR sequences (C). Coronal brain MRI showed hypointensity in the deep cerebellar white matter on T1W imaging (D).

Figure 3

Clinical examination findings in CTX. Note the presence of tendon xanthoma (white arrows) located in the Achilles tendon (A) and the anterior tibial tuberosity (B). Adapted and modified with permission from [3].