Case Report
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2020; 8(21): 5446-5456
Published online Nov 6, 2020. doi: 10.12998/wjcc.v8.i21.5446
Chinese patient with cerebrotendinous xanthomatosis confirmed by genetic testing: A case report and literature review
Lan-Xiao Cao, Mi Yang, Ying Liu, Wen-Ying Long, Guo-Hua Zhao
Lan-Xiao Cao, Mi Yang, Guo-Hua Zhao, Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China
Ying Liu, Wen-Ying Long, Central Laboratory, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China
Author contributions: Cao LX analyzed the data and drafted the manuscript for intellectual content; Yang M played a major role in the acquisition of data; Liu Y interpreted the patient data; Zhao GH and Long WY revised the manuscript for intellectual content; All authors read and approved the final manuscript.
Supported by Zhejiang Province Medical Science and Technology Project, No. 2020RC061 and No. 2019ZD021; Jinhua Bureau of Science and Technology Project, No. 2020-3-004.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no competing interests.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guo-Hua Zhao, MD, Doctor, Department of Neurology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, N1 Shangcheng Avenue Yiwu, Yiwu 322000, Zhejiang Province, China. gzhao@zju.edu.cn
Received: July 15, 2020
Peer-review started: July 17, 2020
First decision: August 8, 2020
Revised: August 9, 2020
Accepted: September 23, 2020
Article in press: September 23, 2020
Published online: November 6, 2020
Processing time: 113 Days and 21.2 Hours
Abstract
BACKGROUND

Cerebrotendinous xanthomatosis (CTX) is a treatable autosomal recessive inherited metabolic disorder. It results from a deficiency of sterol 27-hydroxylase (CYP27A1), which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis. Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain, eyes, tendons, and vessels, resulting in juvenile cataracts, tendon xanthoma, chronic diarrhea, cognitive impairment, ataxia, spastic paraplegia, and peripheral neuropathy. CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.

CASE SUMMARY

A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied. The patient is a 47-year-old male, who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts, cerebellar ataxia, pyramidal signs and chronic diarrhea. There was a significant increase in the concentration of free fatty acid compared to normal range. Doppler ultrasound of the urinary system showed multiple left kidney stones, a right kidney cyst, and a hypoechoic area in the bladder, which could move with body position. Sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon, abnormal thickening of the plantar fat, and a small amount of exudation around the fascia in front of the Achilles tendon. Cerebral MRI suggested white matter (WM) demyelination and slight cerebral atrophy. The diagnosis was confirmed by targeted sequencing, which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T, c.1263+1G>A). Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid. Sediments in the bladder disappeared after therapy.

CONCLUSION

CYP27A1 genetic analysis should be the definitive method for CTX diagnosis. This case suggests that urinary system diseases may be neglected in CTX patients. The clinical, biological, radiological, and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.

Keywords: Cerebrotendinous xanthomatosis; CYP27A1; Clinical; Genetic; Cholestanol; Case report; Metabolic diseases

Core Tip: Cerebrotendinous xanthomatosis (CTX) is a metabolic disorder inherited in an autosomal recessive manner. A total of 520 CTX case reports published in the literature worldwide are reviewed to promote a better understanding of the clinical and genetic characteristics of CTX. Cataract is the most common symptom with a frequency of 80.37%, and xanthoma is the second most common systemic symptom of CTX. In all, 56.57% of patients showed electroencephalogram abnormalities including diffuse slowing, and 76.72% had abnormal magnetic resonance images. Bilateral hyperintensity of the dentate nuclei and surrounding white matter on T2 and fluid-attenuated inversion recovery sequences is considered a representative radiological feature of CTX.