Abstract
Background: Classic cerebrotendinous xanthomatosis (CTX; OMIM #213700) manifests itself in childhood with chronic diarrhea, juvenile cataracts, tendon xanthomas and neurological symptoms. Biallelic inactivation of CYP27A1 is responsible for cholesterol 27-hydroxylation, leading to cholestanol accumulation in the central nervous system, eyes and tendons. Less commonly, the disease can present in young adults as spastic paraparesis in the absence of xanthomas. Methods: We report on a 28-year old woman diagnosed with CTX who worsened, under treatment, a spinal form of CTX. A review of spinal CTX in the literature is also described. Spinal CTX patients were identified by searching in Pubmed, EMBASE™ and Web of Science databases. Only patients with clinical features of spinal CTX and/or with a typical spinal MRI were included.Results: A woman presented with chronic diarrhea and progressive spastic paraparesis in her twenties. Brain magnetic resonance imaging (MRI) showed cerebral atrophy with diffuse periventricular white matter hyperintensities. Spinal MRI was normal. CYP27A1 gene sequencing confirmed the diagnosis of CTX. Chenodeoxycholic acid (CDCA) treatment was introduced with remission of diarrhea. Treatment was discontinued several times and patient developed psychosis and an ataxospastic gait. Spinal MRI revealed new linear hyperintensities of the corticospinal and gracile tracts, compatible with spinal CTX. Thirty-three patients with spinal CTX were identified in the literature. All patients presented pyramidal signs and 48% dorsal column signs. Juvenile cataracts were described in 78% of patients, chronic diarrhea in 65%, and tendon xanthomas in 31%. Disease improvement or stabilization with chenodeoxycholic acid was observed in 69% of patients. A higher prevalence of the Arg395Cys allele was observed in patients with spinal CTX as compared to CTX in general (ᵡ2; p<0.00001).Conclusions: The diagnosis of spinal CTX can be easily missed or delayed in absence of xanthomas. There is a higher prevalence of the Arg395Cys allele in spinal CTX as compared to classic childhood-onset CTX. CDCA treatment seems to stabilize or improve clinical symptoms in most patients. However, as seen in our patient and in two previously reported cases, sudden interruption of CDCA may lead to irreversible neurological complications.
Increased plasma bile alcohol glucuronides in patients with cerebrotendinous xanthomatosis: effect of chenodeoxycholic acid