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

Frontiers in Neurology · 12 authors, 12 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This case report describes a 60-year-old woman with Cerebrotendinous xanthomatosis (CTX) who presented with a behavioral variant frontotemporal dementia (bvFTD) phenotype, a rare manifestation for this disease. Genetic testing revealed a novel pathogenic mutation in the CYP27A1 gene alongside a known mutation, confirming the diagnosis.

Full summary

938 CHARS

This is a case report of a 60-year-old woman who presented with behavioral and personality changes, including disinhibition, apathy, and compulsive behavior, meeting clinical criteria for probable bvFTD. Neuroimaging showed frontotemporal hypoperfusion and, later, symmetrical high signals in the cerebellar dentate nuclei. Physical examination revealed Achilles tendon xanthomas. Biochemical tests showed elevated serum cholestanol and 7α,12α-dihydroxycholest-4-en-3-one levels. Genetic analysis identified a novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a known pathogenic variant (c.1420C>T, p.Arg474Trp) in the CYP27A1 gene, confirming a diagnosis of CTX. The patient was prescribed chenodeoxycholic acid. The report highlights that CTX can present with an unusual bvFTD phenotype in middle age without classic early-onset symptoms. The authors suggest considering CTX in adults with progressive dementia and xanthomas.

STUDY TYPE

case_report

SPECIALTY

neurology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10029355

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

Frontiers in Neurology

READ THE FULL PAPER

ABSTRACT

Background Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by a mutation in the CYP27A1 gene. Due to the disruption of bile acid synthesis leading to cholesterol and cholestanol accumulation, CTX manifests as premature cataracts, chronic diarrhea, and intellectual disability in childhood and adolescence. This report presents a case of CTX with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age. Case presentation A 60-year-old woman presented with behavioral and personality changes. She showed disinhibition, such as hoarding and becoming aggressive over trifles; compulsive behavior, such as closing doors; apathy; and dietary change. The patient showed a progressive cognitive decline and relatively sparing memory and visuospatial function. She had hyperlipidemia but no family history of neurodegenerative disorders. Initial fluid-attenuated inversion recovery (FLAIR) images showed a high signal in the periventricular area, and brain spectroscopy showed hypoperfusion in the frontal and temporal lobes, mimicking bvFTD. However, on physical examination, xanthomas were found on both the dorsum of the hands and the Achilles tendons. Hyperactive deep tendon reflexes in the bilateral biceps, brachioradialis, and knee and positive Chaddock signs on both sides were observed. Four years later, FLAIR images showed symmetrical high signals in the bilateral dentate nuclei of the cerebellum. Her serum cholestanol (12.4 mg/L; normal value ≤6.0) and 7α,12α-dihydroxycholest-4-en-3-one (0.485 nmol/mL; normal value ≤0.100) levels were elevated. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a known pathogenic variant (c.1420C>T, p.Arg474Trp) of the CYP27A1 gene were found in trans-location. The patient was diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/day). Conclusions This report discusses the case of a middle-aged CTX patient with an unusual phenotype of bvFTD. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) was identified in the CYP27A1 gene. Early diagnosis is important because supplying chenodeoxycholic acid can prevent CTX progression.

CITATION EXPORT

Min Young Chun, Nam Jin Heo, Sang Won Seo et al.. Case report: Cerebrotendinous xanthomatosis with a novel mutation in the CYP27A1 gene mimicking behavioral variant frontotemporal dementia. Frontiers in Neurology. (2023). https://doi.org/10.3389/fneur.2023.1131888

AUTHORS

12 · 12 CENTRES

Min Young Chun, Nam Jin Heo, Sang Won Seo, Hyemin Jang, Yeon-Lim Suh, Ja-Hyun Jang, Young-Eun Kim, Eun-Joo Kim, So Young Moon, Na-Yeon Jung, Sun Min Lee, Hee Jin Kim

1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
2Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea
3Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, Republic of Korea
4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
5Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
6Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea
7Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
8Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
9Departments of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
10Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Republic of Korea
11Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea
12Department of Neurology, Pusan National University Yangsan Hospital, Research Institute for Convergence of Biomedical Science and Technology, Yangsan, Republic of Korea