Delayed diagnosis of cerebrotendinous xanthomatosis with progressive neurological involvement: a case report.

backgroundCerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the CYP27A1 gene. Although effective treatment with chenodeoxycholic acid (CDCA) is available, diagnosis is often delayed due to its heterogeneous clinical manifestations and involvement of multiple organ systems. CASE: We report a 34-year-old man with genetically confirmed CTX who presented with progressive gait instability, dysarthria, dysphagia, and cognitive impairment. His medical history revealed childhood-onset bilateral cataracts, chronic diarrhea, and poor academic performance, while bilateral Achilles tendon masses that developed in adulthood were initially misdiagnosed as benign lipomas. Neurological examination demonstrated cognitive impairment, cerebellar ataxia, and pyramidal signs. Whole-exome sequencing identified a homozygous pathogenic variant in CYP27A1 (NM_000784.4): c.1072 C > T; p.(Gln358Ter), confirming the diagnosis of CTX. After initiation of CDCA therapy (750 mg/day), plasma 7α-hydroxy-4-cholesten-3-one levels decreased markedly, accompanied by improvements in gastrointestinal symptoms, cognition, gait stability, and daily living activities during 6 months of follow-up. However, persistent cerebellar atrophy on follow-up neuroimaging suggested limited reversibility of established neurological damage.

conclusionThis case highlights the importance of recognizing multisystem manifestations of CTX for early diagnosis and timely CDCA therapy.