Published online Nov 6, 2020. doi: 10.12998/wjcc.v8.i21.5446
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
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.
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.
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.
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.