Abstract
Objectives Cerebrotendinous Xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis and is associated with an abnormally high concentration of cholestanol in the blood, neural tissues and tendons that lead to infiltrative pathology.1
Methods A case report.
Results We present a case of a 57-year-old female with a 25-year history of slowly progressive spastic paraparesis. MRI of the neural axis was unremarkable with CSF studies and peripheral neurophysiological studies normal. Transcranial magnetic stimulation showed inexcitable motor corticies bilaterally. An initial clinical diagnosis of primary lateral sclerosis (PLS) or gene-negative hereditary spastic paraparesis was made and treated symptomatically. At 5 years follow-up, the patient had minimal neurological progression and developed right ankle pain with swelling. MRI of the ankle revealed xanthoma infiltration into the Achilles tendon. CTX was considered and genetic testing revealed a homozygous missense variant in exon 5 of the CYP27A1 gene that was deemed novel but considered a variant of uncertain significance (VUS). Phenotyping of this variant with further urine and serum studies demonstrated elevation in cholestanol levels.
Conclusion The diagnosis was thus revised to spinal CTX from a novel pathogenic mutation and the patient was commenced on oral chenodeoxycholic acid with subsequent improvements in biochemical profile.
Reference
Wong JC, Walsh K, Hayden D, Eichler FS. Natural history of neurological abnormalities in cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2018 Jul;41(4):647–656
