The cerebrotendinous xanthomatosis (CTX, OMIM; #213700), known as Bogaert-Scherer-Epstein syndrome or cholestanolosis, was described in 1937 by van Bogaert et al. Further breakthroughs in the understanding of the CTX were set in 1969 and 1991. The first was determining the disease blood plasma marker - cholestanol, and later finding the genetic cause. The disease is inherited in an autosomal recessive pattern (homozygous and compound heterozygotes). CYP27A1mutations (OMIM; *606530) result in 27-sterol-hydroxylase deficiency and reduced production of chenodeoxycholic acid (CDCA). The determination of this metabolic block has led to developing an effective, targeted substitution therapy with CDCA.
The incidence of CTX remains an estimate only. The most extensive population-based study to date predicted that incidence would be 1:134,970 in Europeans, 1:263,222 in Africans, 1:71,677 in Americans, 1:64,267 East Asians, and 1:36,072 in South Asians. Even though CTX is a disease accompanying the patient from birth, the diagnosis is most often made in patients' the early 30s. Based on the available reports, it seems that the disease is not more frequent or clinically different for genders (there are only slight differences in the presence of specific symptoms). However, differences in clinical manifestations are observed between the Asian and non-Asian populations. The overall clinical course of CTX remains highly pleomorphic. This often results in the correct diagnosis being provided with a significant delay, on average 15-25 years.
Despite the broad clinical phenotype of the disease, we can distinguish certain groups of symptoms based on their potential period of onset. For example, cholestatic jaundice, cataracts, and diarrhea are the triad of symptoms that can happen in the first years of life. A child's psychomotor development delay may also accompany them. In some cases, mild dysmorphic features may be present. Other manifestations like tendon xanthomas, ataxia, polyneuropathy, parkinsonism, or osteoporosis occur mainly at the earliest in adolescence.
CYP27A1