In the Thick of It

Our patient had widespread cortical dysfunction, including profound saccadic dysfunction. Leukodystrophy evaluation was planned, including very-long-chain fatty acids, arylsulfatase A, and mitochondrial testing. However, review of a video made during gait testing drew attention to the extreme thickening of her Achilles tendons, making cerebrotendinous xanthomatosis (CTX) the leading diagnostic suspect. Genetic testing revealed a mutation in the CYP27A1 gene, confirming CTX. She underwent cataract surgery and there was immediate improvement in acuity to 20/30 OU. Therapy for CTX was initiated with chenodeoxycholic acid. Within months, she showed significant improvement in cognitive abilities, spontaneous speech, parkinsonism, biparieto-occipital dysfunction, and gait imbalance. Our patient demonstrates classical findings of CTX. Though rare, it is extremely important to diagnose, as this is one of the few treatable leukodystrophies. Further, it has a recognizable pathognomonic sign that can easily be missed on examination - Achilles tendon thickening. Leukodystrophies are a large, heterogeneous group of conditions, which cause significant diagnostic challenges 1. CTX is an autosomal recessive disorder, affecting 3-5 per 100,000 people worldwide, being more common in the Moroccan Jewish population (affecting 1 in 108). CTX is caused by CYP27A1 gene mutations, affecting the enzyme 27-hydroxylase and leading to lowered chenodeoxycholic acid levels. As a result, cholestanol and bile alcohols produce xanthomas and can accumulate in numerous organ systems, including brain, heart, skeletal system and the eyes. Four clinical criteria are used in diagnosis; intractable diarrhea, presenile cataracts, tendinous xanthomas, and neurologic abnormalities (typically in third decade). Particularly suggestive are extrapyramidal disease (81%), cognitive impairment (66%), ataxia (56%), spastic paraparesis, and MRI evidence of dentate nuclei signal alterations 2. Seizures and polyneuropathy are also possible. Ophthalmologic manifestations include bilateral cataracts, optic disc pallor, and palpebral xanthelasma 3-6. Chenodeoxycholic acid is the mainstay of therapy. Early recognition is critical, as delay in therapy is associated with a poor outcome 7.