Cerebrotendinous xanthomatosis is an autosomal recessive lipid storage disorder caused by defects in sterol-27-hydroxylase enzyme in bile acid synthesis.

Clinical presentation

The clinical presentation is highly variable with many potential neurological and other/systemic clinical features ⁶.

• neurological ⁶

  • intellectual disability and cognitive decline in later life

  • peripheral polyneuropathy

  • cerebellar ataxia

  • movement disorders

  • spasticity

  • psychiatric conditions (e.g. depression)

• other/systemic ⁶

  • tendon xanthomas

  • juvenile cataracts

  • diarrhea

  • neonatal jaundice

  • osteoporosis

Pathology

It is an autosomal recessive lipid storage disorder caused by defects in sterol-27-hydroxylase enzyme in bile acid synthesis, which results in β-cholestanol accumulation in various tissues.

Serology

On biochemical studies, the presence of normal or low cholesterol in association with raised cholestanol levels is characteristic.

Radiographic features

Imaging reveals characteristic neuroradiological findings in most patients, but can also reveal evidence of tendon xanthomas (e.g. of bilateral Achilles tendons) and other non-neurological manifestations.

MRI

Common neuroimaging findings include ^1-6:

• cerebral and cerebellar atrophy

• T2 hyperintensities affecting the dentate nuclei (characteristic finding), basal ganglia, cerebral peduncles, cerebellar white matter, and periventricular white matter

  • lesions, particular in the dentate nucleus, may have a T2 hypotintense rim and may have regions of microcalcification

Spinal cord involvement is rare, but can include high T2 signal affecting the lateral corticospinal tracts and dorsal columns ⁸.

Treatment and prognosis

Cerebrotendinous xanthomatosis is a treatable condition. Medical therapy is primarily with chenodeoxycholic acid (CDCA) ⁶.

Differential diagnosis

• Marinesco-Sjogren syndrome