AUTHOR=Nóbrega Paulo Ribeiro , Bernardes Anderson Moura , Ribeiro Rodrigo Mariano , Vasconcelos Sophia Costa , Araújo David Augusto Batista Sá , Gama Vitor Carneiro de Vasconcelos , Fussiger Helena , Santos Carolina de Figueiredo , Dias Daniel Aguiar , Pessoa André Luíz Santos , Pinto Wladimir Bocca Vieira de Rezende , Saute Jonas Alex Morales , Souza Paulo Victor Sgobbi de , Braga-Neto Pedro TITLE=Cerebrotendinous Xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1049850 DOI=10.3389/fneur.2022.1049850 ISSN=1664-2295 ABSTRACT=

Cerebrotendinous Xanthomatosis represents a rare and underdiagnosed inherited neurometabolic disorder due to homozygous or compound heterozygous variants involving the CYP27A1 gene. This bile acid metabolism disorder represents a key potentially treatable neurogenetic condition due to the wide spectrum of neurological presentations in which it most commonly occurs. Cerebellar ataxia, peripheral neuropathy, spastic paraparesis, epilepsy, parkinsonism, cognitive decline, intellectual disability, and neuropsychiatric disturbances represent some of the most common neurological signs observed in this condition. Despite representing key features to increase diagnostic index suspicion, multisystemic involvement does not represent an obligatory feature and can also be under evaluated during diagnostic work-up. Chenodeoxycholic acid represents a well-known successful therapy for this inherited metabolic disease, however its unavailability in several contexts, high costs and common use in patients at late stages of disease course limit more favorable neurological outcomes for most individuals. This review article aims to discuss and highlight the most recent and updated knowledge regarding clinical, pathophysiological, neuroimaging, genetic and therapeutic aspects related to Cerebrotendinous Xanthomatosis.