November 17, 2016
A 40-year-old man with epilepsy since 14 years of age, progressive bilateral lower extremity weakness, and hyperreflexia
Cerebrotendinous Xanthomatosis
- Background:
- Rare autosomal-recessive lipid storage disease with mutation of CYP27A1 gene
- Defects in sterol-27-hydroxylase enzyme in bile acid synthesis, which results in β-cholestanol accumulation with normal or low cholesterol serologic levels
- Clinical Presentation:
- Mean age at onset is 19 years and average age at diagnosis is 35 years
- Mental deterioration with epilepsy
- Spastic-ataxic signs
- Tendon xanthoma (usually bilateral)
- Early bilateral cataracts (precede neurological and tendon xanthoma)
- Key Diagnostic Features:
- Based on clinical findings, biochemical testing, neuroimaging, and molecular genetic analysis
- Cerebellar and cerebral atrophy in 90%
- T2WI and PDWI show high signal lesions in deep grey matter, midbrain, and cerebellar white matter (mostly bilaterally)
- 50% have abnormal high signal intensity in dentate nuclei bilaterally; calcifications may be present.
- T2WI and PDWI show high signal lesions in the posterior and lateral spinal columns (preferentially affected)
- Tendon xanthomas (usually bilateral Achilles tendons) are commonly identified as fusiform thickening and heterogeneous signal.
- Differential Diagnoses:
- Sitosterolemia
- Familial dyslipidemias
- Other inborn errors of bile acid metabolism
- Spinal involvement: subacute combined degeneration, multiple sclerosis, HIV myelitis
- Treatment:
- Chenodeoxycholic acid (CDCA) therapy, lipid-lowering agents
