Polyneuropathy in Cerebrotendinous Xanthomatosis: Diagnostic Challenges and Potential for Therapeutic Intervention

Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disorder caused by mutations in the CYP27A1 gene, leading to cholestanol accumulation in various tissues, including peripheral nerves. Polyneuropathy is an underrecognized feature with considerable variability in clinical presentation and neurophysiological findings in CTX. This review assesses the prevalence, clinical manifestations, and diagnostic methodologies of polyneuropathy in CTX, exploring its underlying mechanisms and potential treatment outcomes. A literature review was conducted using PubMed, Embase, and the Virtual Health Library databases with search terms related to CTX and polyneuropathy. A total of 892 articles were initially identified, with 59 selected for in-depth analysis. The review focused on studies examining peripheral nerve involvement in CTX, including nerve conduction studies, electromyography, and nerve ultrasound. Polyneuropathy in CTX was observed in 50% to 77.7% of patients across multiple case series. Neurophysiological findings varied, with reports of axonal, demyelinating, and mixed polyneuropathies. Clinical presentation included lower limb atrophy, pes cavus, and distal weakness, with sensory symptoms less frequently reported. Treatment with chenodeoxycholic acid (CDCA) showed potential in improving nerve conduction parameters, although the response was variable and dependent on the timing of intervention. Polyneuropathy in CTX presents significant diagnostic challenges due to its heterogeneous presentation and varying neurophysiological findings. Early recognition and intervention are crucial for improving patient outcomes. Peripheral nerve ultrasound is a promising diagnostic tool, complementing traditional neurophysiological assessments. Further research is needed to standardize protocols and explore the full therapeutic potential of CDCA in managing CTX-related polyneuropathy.