Clinical and Radiological Findings of a Cerebrotendinous Xanthomatosis Patient with a Novel p.A335V Mutation in the <i>CYP27A1</i> Gene

Abstract

We herein describe the case of a Japanese cerebrotendinous xanthomatosis (CTX) patient with a novel CYP27A1 gene mutation. The patient had been diagnosed with cataracts at 25 years of age and subsequently developed neurological symptoms in his forties, being referred to our hospital at 47 years of age. Upon admission, Achilles tendon xanthomas, cognitive impairment, dysphagia, dysarthria, dystonia, spasticity, muscle weakness and ataxia were observed. Brain MRI revealed abnormal signals in the dentate nuclei, periventricular white matter and pyramidal tract, and the serum cholestanol level was elevated. A CYP27A1 gene analysis identified compound heterozygosity for p.A335V, a novel mutation, and p.R405Q, a previously reported mutation. Making an early diagnosis of CTX is crucial, as the administration of chenodeoxycholic acid reverses metabolic derangement.

Spinal form cerebrotendinous xanthomatosis patient with long spinal cord lesion

“…8 The other four families were compound heterozygous and all patients showed classic form CTX phenotype. [8][9][10][11] Similar to the p.R405Q mutation, all mutations observed in spinal form CTX were also found in classic form CTX, indicating that none of these mutations is preferentially associated with either the classic or spinal form of the disease. 3,4 Although CTX can mimic neurodegenerative diseases, such as spastic paraplegia and spinocerebellar degeneration, early diagnosis of CTX is crucial because treatment with CDCA reverses metabolic derangement and can prevent or even improve neurological dysfunction.…”

“…8 The p.R405Q mutation was reported previously in five CTX families. [8][9][10][11] Chen et al reported a Japanese family homozygous for p.R405Q mutation, who showed typical CTX manifestations, including tendon xanthomas, cataracts, neurological dysfunctions, elevated serum cholestanol level, and undetectable sterol 27-hydroxylase activities. 8 The other four families were compound heterozygous and all patients showed classic form CTX phenotype.…”

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

“…4b ). p.R405Q in CYP27A1 had previously been reported in three siblings with CTX [ 7 ], and in several Japanese CTX patients [ 5 , 8 ]. p.Q85R had previously been reported as the first mutation identified in all variations of CTX.…”

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). Increased peaks of choline on MR spectroscopy (MRS) have also been observed and may be useful to monitor response to therapy (Degos et al 2016); abnormal lipid peaks have also been detected on MRS, although their clinical significance is uncertain (Embirucu et al 2010).…”