A case series of nine patients with cerebrotendinous xanthomatosis from India and a systematized review of Indian literature.

Introduction: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive congenital disorder of bile acid metabolism resulting from variants in the CYP27A1 gene. CTX presents with heterogenous clinical features. Descriptions from diverse populations remain sparse, particularly from the Indian subcontinent.

Methods: We report a case series of nine Indian patients with CTX, accompanied by a systematized review of Indian literature.

Results: Our case series revealed inter- and intrafamilial heterogeneity. Our review of 36 published cases revealed that most Indian patients presented with neurobehavioral syndromes and spastic ataxia, and parkinsonism and dystonia were considerably rare; 34/36 cases eventually developed cataract, usually in childhood, which was a 'tell-tale' sign. Radiological findings revealed striking dentate T2/FLAIR hyperintensities, periventricular white matter involvement, and involvement of the corticospinal tract, and could detect clinically invisible tendon xanthomas. Missense and frameshift truncation variants were most common in the Indian literature, with the c.525delG variant being encountered most frequently. Several patients received a clinico-radiological/histopathological diagnosis as genetic testing was not performed in all patients. Most patients received ursodeoxycholic acid although it is ineffective in the treatment of CTX.

Conclusion: CTX is a not-to-be-missed treatable ataxia syndrome with heterogeneous clinical features. Parkinsonism and dystonia seem to be less prevalent in Indian cases compared to world literature. Our review also highlights the difficulty in access to, availability of and the urgent need to provide chenodeoxycholic acid in our region, reflected in the small fraction of patients who received this definite treatment despite the 'reversible' nature of the disease.