Cerebrotendinous xanthomatosis presenting with progressive ataxia and dysphonia in a 33-year-old Chinese man: a case report

Abstract Background Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disorder caused by mutations in CYP27A1. Its early signs are nonspecific, and the diagnosis is often delayed for years, by which time neurological damage may be irreversible. We report an adult in whom progressive ataxia and dysphonia led to the diagnosis, and draw attention to the characteristic magnetic resonance imaging (MRI) findings. Case presentation: A 33-year-old Chinese man presented with progressive gait disturbance. Over two years he had developed slowly progressive weakness of both lower limbs, and in the month before admission he began to tire easily on walking. His speech became slurred and his verbal output decreased, progressing to dysarthria, dysphonia, and occasional choking. Examination showed cerebellar ataxia, cognitive impairment, pyramidal signs, peripheral neuropathy, and dystonia, with bilaterally positive Hoffmann and Babinski signs and patellar clonus. Both Achilles tendons were symmetrically enlarged, painless, firm, and fusiform (about 10 cm). Serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol were normal, whereas high-density lipoprotein cholesterol was mildly decreased. Brain MRI showed symmetric bilateral T2 hyperintensities in the cerebellar dentate nuclei, cerebral peduncles, and posterior limbs of the internal capsules, with cerebellar atrophy (Fig. 1). Left ankle MRI showed fusiform swelling of the Achilles tendon with low signal on T1- and T2-weighted images (Fig. 2). Targeted next-generation sequencing with Sanger confirmation revealed compound heterozygous CYP27A1 variants, c.1214G > A (p.Arg405Gln) and c.1435C > T (p.Arg479Cys), confirming CTX. Because chenodeoxycholic acid is unavailable in China, the patient was treated with ursodeoxycholic acid; after four weeks his speech output increased, his responses became more fluent, his Mini-Mental State Examination score rose from 21 to 26, and his lower-limb weakness improved slightly. Conclusions CTX should be considered in adults with progressive ataxia and tendon xanthomas, even when the routine lipid profile is normal. Symmetric T2 hyperintensity of the dentate nuclei is a useful early clue. Because treatment can halt or slow progression, early recognition is essential.