Case report: Cerebrotendinous xanthomatosis with a novel mutation in the CYP27A1 gene mimicking behavioral variant frontotemporal dementia

Front Neurol. 2023 Mar 7;14:1131888. doi: 10.3389/fneur.2023.1131888.

PMID: 36959818

Min Young Chun, Nam Jin Heo, Sang Won Seo

Highlights: This report discusses the case of a middle-aged Cerebrotendinous Xanthomatosis (CTX) patient with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD).

Abstract:

Background: A mutation in the CYP27A1 gene results in Cerebrotendinous Xanthomatosis (CTX), a rare autosomal recessive lipid storage disorder. CTX causes premature cataracts, chronic diarrhea, and intellectual disability in children and adolescents because it interferes with the synthesis of bile acids, which leads to the buildup of cholesterol and cholestanol. This study describes a case of middle-aged behavioral variant frontotemporal dementia (bvFTD) in CTX with an atypical phenotype.

Case presentation: A 60-year-old woman came in with altered behavior and demeanor. She exhibited disinhibition in the form of hoarding and acting out over insignificant things, compulsive behavior in the form of closing doors, apathy, and dietary changes. The patient had gradually deteriorating cognitive abilities but rather normal memory and visuospatial abilities. Despite having hyperlipidemia, she had no ancestors with neurological diseases. The periventricular region had a high signal in the initial fluid-attenuated inversion recovery (FLAIR) images, and brain spectroscopy revealed frontal and temporal lobe hypoperfusion, mimicking bvFTD. On physical examination, xanthomas were seen on the Achilles tendons as well as the dorsum of the hands. Bilaterally, there were hyperactive deep tendon reflexes in the biceps, brachioradialis, and knee as well as positive Chaddock findings. Four years later, FLAIR images of the cerebellum's bilateral dentate nuclei revealed symmetrical high signals. Her blood levels of 7α,12α-dihydroxycholest-4-en-3-one (0.485 nmol/mL; normal value ≤0.100) and cholestanol (12.4 mg/L; normal value ≤6.0) were increased. Two pathogenic variants of the CYP27A1 gene were discovered in trans-location: a novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a well-known pathogenic variant (c.1420C>T, p.Arg474Trp). Chenodeoxycholic acid (750 mg/day) was prescribed after a CTX diagnosis was made for the patient.

Conclusions: The case of a middle-aged CTX patient with an uncommon bvFTD phenotype is discussed in this article. The CYP27A1 gene contains a novel, most likely pathogenic variant (c.1001T>A, p.Met334Lys). Because providing chenodeoxycholic acid can stop CTX progression, early diagnosis is crucial.

Keywords: CYP27A1 gene mutation, behavioral variant frontotemporal dementia, case report, cerebrotendinous xanthomatosis, novel likely pathogenic variant