Objective: To report the type of movement disorders, Neuroimaging, and prognosis in nine adult patients with neurological CTX.

Background: Cerebrotendinous Xanthomatosis (CTX) is a lipid accumulation disorder resulting from a gene mutation in sterol 27-hydroxylase (CYP27A1). Neurological symptoms in CTX are diverse and typically manifest in adulthood.

Method: The research conducted at two centers in Saudi Arabia involved cases that were validated through genetic testing of the CYP27A1 gene.

Results: Nine patients (7 female and 2 male) from four families studied with an average age of 36 (23-42) years were diagnosed and followed up for an average of 5 years (3-9 years). All had start-loss and missense mutations in the CYP27A1 gene, confirmed by Sanger sequencing in two families.

All patient had various movement disorders: Parkinsonism in three patients, kinetic tremor in two patients, oculomotor apraxia in one patient, axial dystonia in one patient, neuropsychiatric in two patients, bulbar weakness and anarthria in one patient, ataxia in two patients, and spastic paraplegia in four patients. Distinct enter and intra-familial variability were markedly noted in all patients, leading to delayed diagnosis by 3-5 years.

Neuroradiological findings demonstrate typical findings: symmetrical T2 hyperintense lesions in periventricular white matter, posterior limb of the internal capsule, globi pallidi cerebral peduncles, substantia nigra, and inferior olive. Also, T2 lesions were seen in cerebellar parenchymal and dentate nuclei and the posterior column of the cervical cord.

Of interest, four patients had no clinical tendon xanthoma, which was detected in Achilles tendon imaging. Very low-density lipoprotein was remarkably elevated in three patients.

Symptomatic management, combined with the extended administration of ChenoDeoxyCholic Acid (CDCA), helped stabilize the neuropsychiatric symptoms in three patients. Unfortunately, three patients passed away before receiving CDCA treatment, and one individual succumbed a year after commencing CDCA therapy. Repeated brain MRI in three patients did not have significant changes.

Conclusion: Movement Disorder manifestations of adult-onset CTX are pleiotropic. In appropriate clinical settings, age of onset, and suggestive radiological observations, screening for pathogenic variants in the CYP27A1 gene is warranted to enable early treatment and to prevent devastating neurological and other disabling sequelae.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/movement-disorders-in-cerebrotendinous-xanthomatosis/