Natural history of neurological abnormalities in cerebrotendinous xanthomatosis.
OBJECTIVES
Cerebrotendinous xanthomatosis (CTX) is a rare inherited neurodegenerative disorder in bile acid synthesis. The natural history of neurological abnormalities in CTX is not well understood. The object of this study was to determine neurological progression in CTX.


METHODS
A literature search on PubMed for "cerebrotendinous xanthomatosis" yielded 91 publications that reported cases of CTX patients. Two independent reviewers abstracted information about the presence and age of onset of neurological abnormalities in published CTX cases. For each neurological abnormality, we estimated the probability of its onset at any given age using cumulative incidence function analysis. We also present our own case series, in which five CTX patients were evaluated.


RESULTS
The literature search yielded 194 CTX cases (ages ranging from newborn to 67 years old). The most common neurological abnormalities were corticospinal tract abnormalities including weakness, hyperreflexia, spasticity, Babinski sign (59.8%), ataxia (58.8%), cognitive decline (46.4%), and gait difficulty (38.1%); 68 (35.0%) had baseline cognitive problems. Cumulative incidence function analysis revealed that ataxia, gait difficulties, and corticospinal tract abnormalities developed throughout life, while cognitive decline tended to develop later in life. Of the less common neurological abnormalities, seizures, psychiatric changes and speech changes developed throughout life, while parkinsonism and sensory changes tended to develop later in life. Our case series corroborated this temporal pattern of neurological abnormalities.


CONCLUSION
We provide estimates for the neurological progression of CTX, categorizing neurological abnormalities according to time and probability of development. Our approach may be applicable to other rare disorders.
['Wong|Janice C|JC|', 'Walsh|Kailey|K|', 'Hayden|Douglas|D|', 'Eichler|Florian S|FS|']
D000328:Adult D000368:Aged D001921:Brain D002635:Chenodeoxycholic Acid D018450:Disease Progression D005260:Female D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D009422:Nervous System Diseases D016896:Treatment Outcome D019294:Xanthomatosis, Cerebrotendinous
Cerebrotendinous xanthomatosis Neurodegenerative disorder Spasticity Ataxia Bile acid synthesis disorder Cataracts Genetic disorder Xanthomas