Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree.
10.3760/cma.j.cn112138-20220328-00215
- Author:
Bo ZHAO
1
;
Zhi Wei WANG
2
;
Yi Mo ZHANG
2
;
Ying Xin YU
2
;
Sheng YAO
2
;
Jin Jing ZHAO
3
;
Hang LI
4
;
Li LIANG
5
;
Shu Yi PAN
6
;
Hai Rong QIAN
7
Author Information
1. Department of Hyperbaric Oxygen, Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China the Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China Senior Department of Neurology, Chinese PLA General Hospital, Beijing 100853, China.
2. Senior Department of Neurology, Chinese PLA General Hospital, Beijing 100853, China.
3. Department of Neurology, the 305th Hospital of the People's Liberation Army, Beijing 100017, China.
4. Department of Hyperbaric Oxygen, Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.
5. Senior Department of Neurology, Chinese PLA General Hospital, Beijing 100853, China Navy Clinical College, the Fifth School of Medicine, Anhui Medical University, Hefei 230032, China.
6. Department of Hyperbaric Oxygen, Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China the Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
7. the Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China Senior Department of Neurology, Chinese PLA General Hospital, Beijing 100853, China Navy Clinical College, the Fifth School of Medicine, Anhui Medical University, Hefei 230032, China.
- Publication Type:Journal Article
- MeSH:
Humans;
Male;
Adult;
Female;
Xanthomatosis, Cerebrotendinous/pathology*;
Pedigree;
Cholestanetriol 26-Monooxygenase/genetics*;
Mutation;
Ataxia
- From:
Chinese Journal of Internal Medicine
2023;62(4):401-409
- CountryChina
- Language:Chinese
-
Abstract:
Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
