Cerebrotendinous Xanthomatosis: A Critical Update

Cerebrotendinous xanthomatosis (CTX) also known as van Bogaert–Scherer–Epstein syndrome, Thiebaut’s syndrome and cerebrotendinous cholesterosis, is an autosomal-recessive lipid-storage disease characterized by the triad of juvenile cataracts, tendon xanthomas and progressive neurodegeneration. Excess cholesterol and cholestanol are deposited in multiple organs, including the cerebrum, cerebellum, lens and tendons. Approximately 300 cases are reported worldwide, but it is suspected that the incidence of CTX is underestimated. The disease is attributed to approximately 50 mutations in the CYP27A1 gene coding for the enzyme sterol 27-hydoxylase, which is responsible for initial oxidation of the side chain of the cholesterol molecule in bile acid biosynthesis. CTX has varied clinical presentations, but no genotype–phenotype relationship has been documented. In some intrafamilial cases, clinical presentations may vary considerably. MRI for CTX is sensitive for diagnosis and classically demonstrates cerebral and cerebellar atrophy and xanthomatous lesions preferentially affecting the dentate nuclei. Patients have high serum levels of cholestanol with normal total cholesterol and increased urinary excretion of bile acids. Treatment of patients with chenodeoxycholic acid, particularly when used along with HMG-CoA reductase inhibitors (statins) or low-density lipoprotein apheresis, can normalize cholestanol levels as well as prevent further degeneration. Therefore, the need for early diagnosis is well documented in the literature, as it prevents the significant morbidity and mortality associated with this disease.