Natural history of neurological abnormalities in cerebrotendinous xanthomatosis

J Inherit Metab Dis 2018 Jul;41(4):647-656. doi: 10.1007/s10545-018-0152-9.

PMID: 29484516

Janice C Wong, Kailey Walsh, Douglas Hayden

Highlights: The object of this study was to determine neurological progression in CTX. 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.

Abstract

Objectives: Cerebrotendinous xanthomatosis (CTX) is a rare hereditary neurodegenerative disorder in bile acid synthesis. The natural course of CTX-related neurological abnormalities is unclear. The goal of this study was to identify neurological progression in CTX.

Methods: A PubMed search for "cerebrotendinous xanthomatosis" turned up 91 papers with cases of CTX patients. In reported CTX cases, two independent reviewers extracted information about the presence and age of onset of neurological disorders. Using cumulative incidence function analysis, we calculated the likelihood of each neurological abnormality presenting at any given age. We also offer our own case series, which included five CTX patients.

Results: The literature search turned up 194 CTX cases (ages ranging from newborn to 67 years old). Corticospinal tract abnormalities, such as weakness, hyperreflexia, spasticity, Babinski sign (59.8%), ataxia (58.8%), cognitive decline (46.4%), and gait difficulty (38.1%), were the most frequent neurological abnormalities; 68 (35.0%) had baseline cognitive impairments. Ataxia, gait difficulties, and corticospinal tract abnormalities developed throughout life, whereas cognitive decline tended to emerge later in age, according to a cumulative incidence function study. 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. This chronological pattern of neurological problems was confirmed in our case series.

Conclusion: We give estimations for CTX's neurological progression, classifying neurological disorders by time and likelihood of development. Our method might be applicable to other uncommon diseases.

Keywords: Ataxia, Bile acid synthesis disorder, Cataracts, Cerebrotendinous xanthomatosis, Neurodegenerative disorder, Spasticity, Xanthomas