Chinese patient with cerebrotendinous xanthomatosis confirmed by genetic testing: A case report and literature review

World J Clin Cases. 2020 Nov 6;8(21):5446-5456. doi: 10.12998/wjcc.v8.i21.5446.

PMID: 33269283 Lan-Xiao Cao, Mi Yang, Ying Liu, Wen-Ying Long, Guo-Hua Zhao

Summary: This article is a case study that includes a Chinese family with Cerebrotendinous xanthomatosis (CTX) which had one patient and four heterozygous carriers. The clinical, biological, radiological, and genetic characteristics of CTX are summarized in order to aid in early detection and treatment. This study emphasizes that genetic analysis of the CYP27A1 gene should be the gold standard for CTX diagnosis.

Abstract

Background: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic condition that can be treated. It is caused by a lack of the mitochondrial cytochrome P450 enzyme, sterol 27-hydroxylase (CYP27A1), which catalyzes cholesterol hydroxylation and regulates cholesterol homeostasis. Patients with CYP27A1 deficiency experience symptoms such as juvenile cataracts, tendon xanthoma, chronic diarrhea, cognitive impairment, ataxia, spastic paraplegia, and peripheral neuropathy as a result of excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain, eyes, tendons, and arteries. CTX is underdiagnosed because most information about the illness is based on case reports.

Case Summary: This study includes a Chinese family with CTX that had one patient and four heterozygous carriers. The patient is a 47-year-old man with mainly psychiatric symptoms but no cataracts, cerebellar ataxia, pyramidal signs, or chronic diarrhea, which are all cardinal features of CTX. When compared to the normal range, the concentration of free fatty acid increased significantly. Multiple left kidney stones, a right kidney cyst, and a hypoechoic region in the bladder that could move with body position were discovered using Doppler ultrasound of the urinary system. The right Achilles tendon and upper medial malleolus flexor tendon appeared enlarged on sagittal and axial magnetic resonance imaging (MRI) of the right ankle joint, with aberrant thickening of the plantar fat and a little amount of exudation around the fascia in front of the Achilles tendon. White matter (WM) demyelination and mild brain atrophy were found on a cerebral MRI. Targeted sequencing validated the diagnosis, revealing compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene (c.435G>T and c.1263+1G>A). His psychiatric symptoms improved and his serum free fatty acid levels were normalized after three weeks of treatment with a combination of lipid-lowering and antipsychotic therapy. After therapy, the sediments in the bladder were gone.

Conclusion: The genetic analysis of the CYP27A1 gene should be the gold standard for CTX diagnosis. This case demonstrates that in CTX patients, urinary system diseases may be neglected. In this study, the clinical, biological, radiological, and genetic characteristics of CTX are summarized in order to aid in early detection and treatment.

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