Objective:

To highlight key clinical and diagnostic considerations that help adult neurologists to identify cerebrotendinous xanthomatosis (CTX).

Background:

CTX is a rare autosomal recessive lipid storage disease caused by a pathogenic variant in CYP27A1 gene, which disrupts bile acid synthesis. The resulting deficiency in sterol-27-hydroxylase leads to cholesterol buildup. Systemic and neurological symptoms vary and can include cataracts, xanthomas, cognitive decline, seizures, and movement disorders.

Design/Methods:

We present a 42-year-old male with history of hypoxic brain injury at birth. He was diagnosed with epilepsy and new-onset tremors at age 14. By age 37, he was found to have cataracts, along with worsening speech and gait changes. He presented to the movement disorder clinic at age 40 with ataxia and worsening gait disturbances. MRI of the brain showed cerebellar atrophy and symmetric T2 Flair abnormalities in the brainstem and cerebellum. Imaging differential diagnoses included hypoxic injury versus a leukodystrophy. Working diagnosis included a progressive ataxia syndrome. He was monitored until he had acute changes and hospitalization two years later, presenting new cognitive difficulties and an inability to walk independently.

Results:

A comparison review from three years ago of the brain and spine MRI indicated evolving cerebral atrophy, posterior white matter changes in the internal capsule, ventral midbrain, pons, and spinal cord alterations. Based on the patient's history and progressive clinical course, a leukodystrophy became a primary consideration. The leukodystrophy genetic panel revealed Cyp 27A1 (associated with CTX) and c.767T>C.

Conclusions:

CTX disease manifestations can potentially be prevented through early initiation of replacement therapy with Chenodeoxycholic acid. Symptoms often start during childhood, but there is frequently a delay in diagnosis. It remains a crucial consideration for adult neurologists when patients present with early cataracts, T2-FLAIR hyperintense lesions in the dentate nucleus and surrounding white matter, and various neurological signs and symptoms.