cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a disorder of bile acid synthesis that affects multiple systems including the liver, eyes, tendons, and brain. It is caused by pathogenic variants in the CYP27A1 gene, which disrupts normal bile acid production and leads to the accumulation of cholestanol. Affected individuals often present with neonatal cholestasis and childhood-onset cataracts, progressing to tendon and brain xanthomas with neurologic dysfunction in adulthood. Precise prevalence estimates are not well established.

Individuals with cerebrotendinous xanthomatosis typically exhibit a consistent set of clinical features. Characteristic findings include lower limb muscle weakness, cerebral atrophy, an abnormal Babinski sign, and tendon xanthomatosis. Additional features such as cerebellar atrophy, gait disturbances, elevated cerebrospinal fluid cholestanol concentration, abnormal EEG with generalized slow activity, and ankle clonus are invariably observed. Not all individuals experience all features, and severity varies considerably.

Cerebrotendinous xanthomatosis is caused by pathogenic variants in the CYP27A1 gene, which plays a crucial role in bile acid synthesis. Disruption of this gene leads to abnormal bile acid metabolism and the deposition of cholestanol in various tissues, contributing to the clinical manifestations. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual inherits two defective copies of the gene, one from each parent. Families are encouraged to seek genetic counseling to better understand inheritance and reproductive options.

Currently, management of cerebrotendinous xanthomatosis focuses on supportive care and symptom management, as there are no FDA-approved treatments available. Treatment is individualized and typically involves a multidisciplinary team to address neurological, musculoskeletal, and systemic issues. Regular monitoring through physical and occupational therapy, along with other supportive interventions, forms an important part of care. Patients should discuss treatment options with their healthcare team and consider genetic counseling to explore family planning and long-term management.

The clinical course of cerebrotendinous xanthomatosis varies significantly among affected individuals. Many experience a lifelong trajectory with early symptoms progressing to neurological dysfunction later, although the severity and rate of progression differ considerably. With current standards of care, many individuals achieve a period of stabilization, and outcomes continue to improve as management strategies evolve. Outcomes described in medical literature continue to evolve as standards of care improve; families often find it helpful to connect with genetic counselors and specialists experienced in this condition.

Several clinical trials are currently investigating new treatment approaches for cerebrotendinous xanthomatosis. Individuals interested in exploring research opportunities can search ClinicalTrials.gov or consult their care team about eligibility.