CTX is caused by mutations in the CYP27A1 gene

CTX is caused by mutations in the CYP27A1 gene, which codes for the mitochondrial enzyme 27-hydroxylase^1,2

27-hydroxylase catalyzes a critical step in the acidic pathway for cholesterol elimination via conversion to bile acids in the liver.^1,2

CYP27A1 mutations prevent critical steps in bile acid synthesis resulting in cholestanol accumulation²

In CTX, sterol 27-hydroxylase deficiency reduces the production of cholic acid and chenodeoxycholic acid (CDCA)—the most common endogenous bile acids.^1,3,4 Because bile acids are inhibitors of CYP7A, this negative feedback mechanism is lost and the process of cholesterol elimination is interrupted. This leads to increased levels of bile alcohols and other bile acid precursors including 7α, 12α-Dihydroxy-4-cholesten-3-one and accumulation of cholestanol and cholesterol throughout the body with toxic effects.^1,2,5

Mechanism of CTX^1-3,5