Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of
cholesterol metabolism. It presents with systemic and neurological symptoms, rarely including
parkinsonism. Presented here are a clinical description of a new family with
cerebrotendinous xanthomatosis and
parkinsonism and a review of 13 additional cases reported in the literature. The index case developed
corticobasal syndrome, previously not reported in
cerebrotendinous xanthomatosis. His brother had
parkinsonism with cerebellar features and
cognitive impairment. In a literature review, median age of onset of
parkinsonism was found to be 40 years. Nearly all patients had other neurological
symptoms: cognitive (93%), pyramidal (93%), or cerebellar (53%). All patients had walking difficulties, with falls in 27%. Systemic features were common:
cataracts (93%) or tendon xanthomata (87%). Frequent MRI abnormalities included cerebellar
atrophy (100%), cerebral
atrophy (80%), and dentate nuclei signal changes (80%). Functional dopaminergic imaging often demonstrated presynaptic
denervation. Improvement with
levodopa was frequent (91%) but mild. Progressive neurological decline occurred in 92% of patients despite treatment with
chenodeoxycholic acid.
Cerebrotendinous xanthomatosis should be considered in the differential diagnosis of atypical
parkinsonism, including
corticobasal syndrome, particularly with early age of onset and in the context of a complex neurological phenotype. Tendon xanthomata, early-onset
cataracts, and radiological findings of cerebellar
atrophy with lesions of the dentate nuclei are useful clinical clues. Symptomatic treatment with
levodopa may help, but progressive neurological decline is frequent despite treatment with
chenodeoxycholic acid.