Suspected pathophysiologic mechanism
Cerebrotendinous xanthomatosis (CTX) is a rare inborn bile acid synthesis disorder. It is caused by CYP27A1mutations, which are responsible for a deficiency of one key enzyme (27-hydroxylase) in the cholesterol metabolic pathway.
The result is almost complete inhibition of chenodeoxycholic acid (CDCA) production, and to a lesser extent, of cholic acids. The lack of these products means that the body, feeling their deficiency, drives the metabolic pathway to further their production.
Unfortunately, intermediate products of the path cannot be converted to their final form due to an inactive enzyme, so they undergo emergency metabolism. That creates many products toxic to cells, including cholestanol. This way, excessive cholestanol and other redundant metabolites are deposited in specific tissues.
As a result, clinical symptoms develop from various organs due to the surrounding tissue damage or the growth of deposits to large s.
Type of mutations
The CYP27A1gene is located in chromosome locus 2q35 and consists of 9 exons and 8 introns. Currently, over 114 pathological variants were described for all exons and introns. The disease is inherited regardless of gender, and for symptoms to develop, both copies of the CYP27A1gene must be affected (autosomal recessive inheritance). CYP27A1gene loss-of-function mechanism is responsible for development of clinical signs in CTX.
CYP27A1