Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid

Abstract

Background: Cerebrotendinous xanthomatosis (CTX) is a rare but treatable neurometabolic disorder of lipid storage and bile acid synthesis. Whilst CTX is said to present with the classic triad of juvenile onset cataracts, tendon xanthomata and progressive ataxia, the diversity of presentation can be such that the diagnosis may be substantially delayed resulting in permanent neurological disability.

Methods: A retrospective review of the clinical characteristics and imaging findings of 4 patients with CTX presenting to the Sheffield Ataxia Centre over a period of 25 years.

Results: Although CTX-related symptoms were present from childhood, the median age at diagnosis was 39 years. Only 1 of the 4 cases had tendon xanthomata, only 2 cases had juvenile onset cataracts and 3 had progressive ataxia with one patient presenting with spastic paraparesis. Serum cholestanol was elevated in all 4 patients, proving to be a reliable diagnostic tool. In addition, cholestanol was raised in the CSF of 2 patients who underwent lumbar puncture. Despite treatment with chenodeoxycholic acid (CDCA) and normalization of serum cholestanol, CSF cholestanol remained high in one patient, necessitating increase in the dose of CDCA. Further adjustments to the dose of CDCA in the patient with raised CSF cholestanol resulted in slowing of progression. Two of the patients who have had the disease for the longest continued to progress, one subsequently dying from pneumonia.

Conclusion: A high index of suspicion for CTX, even in the absence of the classical triad is essential in reaching such diagnosis. The earlier the diagnosis and treatment, the better the outcome.

Keywords: Ataxia; CTX; CYP27A1; Cerebrotendinous xanthomatosis; Chenodeoxycholic acid; Cholestanol; Early onset cataracts; Tendon Xanthomata.

Fig. 1

Axial T2 weighted imaging of patient 1, showing bilateral hyper intense lesions involving the dentate nuclei and the deep cerebellar white matter (a). Supratentorial imaging (Patient 2) shows white matter tract involvement, specifically of the corticospinal tract and optic radiation (b)

Fig. 2

CT (a) and MRI (b) images from Patient 3 showing evidence of cerebellar calcification which although rare can be a feature of CTX

Fig. 3

Axial T2 MRI spinal images (Patient 4) showing signal changes affecting mainly lateral Corticospinal tracts (magnified in image b)