Cerebrotendinous xanthomatosis: clinical and imaging clues of a rare treatable cause of ataxia

Abstract

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal-recessive lipid storage disease.1 We present the case of a man in his 40s (patient 1) with a prior history of persistent childhood diarrhoea and cognitive-developmental delay. The patient presented to our neurology outpatient clinic with a 10-year history of progressive gait impairment and recent episodes of falls. The patient has one healthy brother and three sisters, two of whom (labelled as patients 2 and 3) also manifested cognitive impairment-see figure 1. All impaired siblings reported cataract extraction before the age of 20. Patient 2 had previously complained of ankle swelling in an orthopaedic evaluation 15 years earlier and performed ankle-joint MRI, deemed inconclusive. On examination, all patients exhibited low stature, appendicular ataxia, pyramidal signs and broad-based ataxic gait. Patient 2's lower limb examination also showed marked pes cavus, clawing of the toes and Achilles' tendon xanthomas (figure 2A). Brain MRI sagittal T1-weighted image revealed cerebellar atrophy (figure 2B) and axial T2-weighted image displayed hyperintensities within the dentate nuclei (figure 2C) in patient 1. The combination of cerebellar ataxia, early-onset cataracts and tendon xanthomas prompted testing for serum cholestanol, which was significantly raised (patient 1: 119 μmol/L; patient 2: 120 μmol/L; patient 3: 84 μmol/L, N: 3.5-23.8 μmol/L). Screening for variations on the CYP27A1 gene revealed two heterozygous variants (c.1420C>T, p.(Arg474Trp)) and (c.1016C>T, p.(Thr339Met)). These variants were previously reported as pathogenic, which confirmed CTX suspicions. All patients started therapy with chenodeoxycholic acid (CDCA). At the 6-month follow-up, patient 1 reported noticeable improvement in balance.