Movement disorders in cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is an inborn error of cholesterol and bile acid metabolism, leading to neuropsychiatric and systemic manifestations. Movement disorders have rarely been reported in CTX, while a detailed appreciation of the full phenotypic spectrum is required in order to prevent underdiagnosis of this disease. This review focuses on the frequency of more unusual, non-ataxia and non-spasticity movement disorders reported in CTX. In total, 39 articles were reviewed, describing 55 CTX patients with a movement disorder. Additionally, we report on seven patients with parkinsonism out of our Dutch cohort of 79 (77 genetically proven) CTX patients. Mean age at onset of the movement disorder was 40 ± 12 years (median 40, range 13-62 years). Movement disorders can be considered a late disease manifestation. Parkinsonism was the most frequently reported movement disorder, followed by dystonia, myoclonus and postural tremor. Movement disorders were found to be mixed in 23% of patients and were usually part of a complex clinical picture, rather than a prominent symptom. Still, in 18% of the cases, a movement disorder was the presenting symptom. Unusual movement disorders represent a rare clinical feature in CTX, but CTX should be considered in the differential diagnosis of these movement disorders, particularly in case of early onset, and when associated with other neurological features (especially cognitive impairment, pyramidal and cerebellar signs) and/or with systemic features (such as diarrhoea, cataract and tendon xanthomas). CTX is a treatable disorder, stressing the importance of considering CTX as a potential cause of movement disorders.