Cerebrotendinous Xanthomatosis is a rare autosomal recessive lipid storage disease following the Mendelian inheritance pattern. It is caused by mutations in a gene encoding a cytochrome P450 oxidase predominantly involved in the biosynthesis of bile acids from cholesterol. The lack of the functional enzyme results in a reduced production of some components of bile, as well as accumulation of cholestanol and cholesterol in different tissues, e.g., brain, tendons, lenses, bones and vessels.

CTX has a variety of clinical manifestations, including chronic diarrhoea, developmental cataract, xanthomas, neurological features, psychiatric manifestations, premature atherosclerosis and hypothyroidism. The diagnosis is confirmed by laboratory investigations including biochemical tests, brain imaging and molecular analysis. CTX is considered rare, but it is also believed to be underdiagnosed worldwide due to late, gradual and often variable onset of signs and symptoms. The Epiomic™ database presents the projected prevalent CTX case load for 2017–2027.

The prognosis of CTX largely depends on how early the disorder is diagnosed and therapy initiated. Preventing the accumulation of cholestanol can prevent, delay and/or limit the onset of signs and symptoms. The therapy also has some ability to improve and reverse symptoms that have already occurred, with neurological symptoms being the most difficult to improve.

The most commonly used CTX therapy is chenodeoxycholic acid (CDCA) that treats the symptoms by reducing the synthesis and plasma levels of cholestanol. In the long-term setting, it is used alone or in combination with inhibitors of HMG-CoA reductase. Among the comorbidities of CTX are cataracts, intellectual impairment, seizures, tendon xanthomas, osteoporosis and diarrhoea, all of which are treated individually. The Epiomic™ database contains a forecast of the estimated population with these comorbidities.

Quick Fact

To date, more than 50 mutations of various types have been identified in the CYP27A1 gene, with some patients carrying more than one of them. No genotype–phenotype correlations have been identified, and the phenotypic manifestation can vary even between identical twins.