Rare lipid storage disorder mimicking neurological condition highlights diagnostic challenges

Cerebrotendinous xanthomatosis (CTX) can present with atypical and misleading symptoms, leading to diagnostic delays, according to a recent case report that shed light on the complexities of diagnosing and managing this condition.

A comprehensive approach combining clinical evaluation, imaging, genetic testing, and biochemical analyses is essential for accurate diagnosis and effective management, particularly in cases with uncommon presentations.

The case involves a 53-year-old woman with a 25-year history of slowly progressive spastic paraparesis, initially misdiagnosed as hereditary spastic paraplegia. After 5 years, new symptoms emerged, including right ankle swelling. Imaging revealed Achilles tendon enlargement consistent with xanthoma infiltration. Genetic testing uncovered a homozygous variant of uncertain significance in the CYP27A1 gene, while biochemical tests confirmed CTX through elevated cholestanol levels and cholestanepentol glucuronide in urine.

Treatment with chenodeoxycholic acid stabilized her condition over three years, though her advanced disease stage limited improvements in mobility.

Reference
O’Keefe E, Kiernan M, Huynh W. Cerebrotendinous xanthomatosis: A complex interplay between a clinically and genetically heterogeneous condition. Eur J Neurol. 2025;32(1):e70006. doi: 10.1111/ene.70006. PMID: 39760285; PMCID: PMC11702487.