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

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.

CYP27A1 mutation in a case of cerebrotendinous xanthomatosis: A case report

“…The typical imaging findings indicating the prevalence of CTX include T2-weighted and FLAIR imaging hyperintensity in the dentate nucleus[ 10 ]. The current case supports the inclusion of high signal intensity of the two dentate nuclei on MRI as a typical feature of CTX[ 11 ]. The typical imaging manifestations of CTX are high signal in T2 weighted imaging and FLAIR imaging of dentate nucleus.…”

Cerebrotendinous xanthomatosis with tremor as the main manifestation: A case report

“…Parkinson’s syndrome is less common and usually appears at an older age. [17] The clinical manifestations observed in our patient are rare among individuals with CTX, with epilepsy as the initial manifestation, and her main symptoms were head and body tremors, and there are no reports of these manifestations. Some studies have pointed out that epilepsy and Parkinson’s syndrome are the first neurological manifestations of CTX.…”

First case series of Polish patients with cerebrotendinous xanthomatosis and systematic review of cases from the 21st century

“…During the systematic review, 568 cases of CTX patients were identified. 5,6,8,9,11,13, In this cohort, 392 cases were genetically confirmed, with 114 different CYP27A1 pathogenic variants. We also distinguished between a cohort of patients of Asian and non-Asian origin in order to highlight any differences between them.…”

“…These symptoms usually are present late, at patients 30s-40s. 11,96 Cohort studies report incidence at 59.0%-90.0% of pyramidal-cerebellar dysfunction and 18.6%-19.0% of speech changes. 19,20,37 We found that ataxia and/or spastic paraparesis were present in 68.71% of patients and speech impairment at 36.49% of patients.…”

“…observation seems highly probable. 11 Thanks to Salen et al and further investigations, CTX is currently one of the few inherited neurometabolic disorders amenable to a specific treatment. 12 Without appropriate treatment, the disease progresses, being potentially debilitating or lethal.…”