Late-onset spinal form xanthomatosis without brain lesion: a case report

Abstract

BackgroundCerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase (CYP27A1) gene. Patients with typical CTX show neurological dysfunction including bilateral cataracts, paresis, cerebral ataxia, dementia, and psychiatric disorders, and magnetic resonance imaging (MRI) has revealed symmetrical lesions in the cerebellar white matter.Case presentationWe report the case of a patient with late-onset spinal form CTX without brain lesion. He showed pyramidal tract signs, and impaired joint position and vibration sensation in the lower limbs. Cervical sagittal MRI demonstrated a longitudinally extensive white matter abnormality in the dorsal column of the C2-C7 spinal cord; however, a brain MRI revealed an absence of lesions, including in the cerebellar white matter. Genetic analysis of CYP27A1 revealed that the patient was compound heterozygous for p.Gln85Arg in exon 1, a novel mutation, and p.Arg405Gln in exon 7, a previously reported mutation.ConclusionThis is the first report of late-onset spinal form CTX without typical neurological symptoms, and the first report of p.Gln85Arg in CYP27A1. We speculate that spinal form CTX without brain lesion is a clinically and radiologically rare variation of CTX. Therefore, spinal xanthomatosis should be included in the differential diagnosis of chronic myelopathy even with late-onset and/or no other typical neurological findings.

Spinal cerebrotendinous xanthomatosis: A case report and literature review

“…At 42 y: severe spastic tetraparesis, flexum of the 4 limbs, severe dysphagia. 64 Involutive cerebellar and frontal regions, bulbar and CWML NA NA NA p.Val86Glufs30Ter / p.Arg395Cys [ 21 ] 26 M Japan 65 77 + + – + NA 13 (10.4 μg/mL) Normal Cervical dorsal column hyperintensities CDCA 750 mg NA p.Gln85Arg / p.Arg405Gln [ 22 ] 27 F NA 5 52 – NA + + NA Seizures, development delay, dystonia, ataxia, dysarthria, dysphagia, wheelchair at 30y., bedridden at 49 y. 19.6 Cerebral and CWML and atrophy, extensive, symmetric supra and infra-tentorial hyperintensities Central and posterior SCWM, C7 through thoracic vertebra NA NA Confirmed by genetic analysis.…”

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

“…Magnetic resonance imaging (MRI) studies show decreases in total brain volume (particularly gray matter) (Guerrera et al 2010), cerebral and cerebellar atrophy (Pilo de la Fuente et al 2008;Berginer et al 1994), extensive white mater lesions of the spinal cord (in patients with spinal xanthomatosis) (Verrips et al 1999a;Yanagihashi et al 2016), and bilateral hyperintensity of the dentate nuclei and surrounding white matter (considered characteristic of CTX; Fig. 3) (De Stefano et al 2001;Guerrera et al 2010;Yoshinaga et al 2014).…”

A Late-onset and Relatively Rapidly Progressive Case of Pure Spinal Form Cerebrotendinous Xanthomatosis with a Novel Mutation in the <i>CYP27A1</i> Gene

“…Spinal form CTX is a rare clinical subgroup of CTX, and 18 patients have been reported to date ( 4 - 8 , 12 , 13 ). The age of onset ranged from 10 to 40 years, and all patients showed slowly progressive myelopathy, including motor and sensory disturbance of the lower legs ( 12 ).…”

“…Spinal form patients chiefly display chronic myelopathy (4). Recently, pure spinal form CTX patients have been reported to only show a slowly progressive myelopathy (4)(5)(6)(7)(8), and such patients are typically misdiagnosed with hereditary spastic paraplegia. We herein described a late-onset, relatively rapidly progressive pure spinal form CTX patient with a novel variant in the CYP27A1 gene.…”