对脑黄瘤病的临床、生化和分子研究:一项针对 100 名土耳其人的全国性研究

IF 3.7 2区 生物学 Q2 ENDOCRINOLOGY & METABOLISM Molecular genetics and metabolism Pub Date : 2024-05-13 DOI:10.1016/j.ymgme.2024.108493
Tanyel Zubarioglu , Ertuğrul Kıykım , Engin Köse , Fatma Tuba Eminoğlu , Pelin Teke Kısa , Mehmet Cihan Balcı , Işıl Özer , Aslı İnci , Kübra Çilesiz , Ebru Canda , Havva Yazıcı , Burcu Öztürk-Hişmi , Fatma Derya Bulut , Sevil Dorum , Abdurrahman Akgun , Gül Yalçın-Çakmaklı , Gonca Kılıç-Yıldırım , Erdoğan Soyuçen , Aylin Akçalı , Dilek Güneş , Çiğdem Aktuğlu-Zeybek
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引用次数: 0

摘要

目的脑膜黄瘤病(CTX)是一种遗传性代谢性疾病,以进行性神经系统和神经系统外症状为特征。这项回顾性、描述性研究旨在探讨 CTX 的发病时间和诊断时间,并根据土耳其全国范围内的一系列综合患者资料,扩展 CTX 的表型和基因型。回顾了分子分析数据、发病和诊断年龄、诊断延迟、神经系统和神经系统外症状、诊断时的血浆胆固醇水平、脑磁共振成像和肌电图结果。诊断时的平均年龄为(28.16 ± 14.28)岁,诊断延迟时间为(18.39 ± 13.71)年。36 名患者在儿童时期被确诊。两组患者意向性震颤(p = 0.069)、周围神经病变(p = 0.234)和精神表现(p = 0.396)的发生率没有差异,表明儿童患者的发病率较高。三名成年患者表现较轻,没有神经系统受累。七名患者尽管有神经系统损伤,但血浆胆甾醇水平正常。对 CYP27A1 基因的测序发现了 25 个不同的变异体,其中有一个新的 c.671_672del 变异体以前未在文献中描述过。结论根据对土耳其 CTX 队列的观察,我们强调 CTX 的真实发病率可能被低估了,即使没有神经系统损伤,它也有广泛的临床表型。在儿童中,小脑异常发现、周围神经病变和与智力障碍相关的精神症状被认为是避免诊断延误的警示信号。在临床怀疑的病例中,尽管血浆胆甾醇水平正常,但仍建议进行分子分析,因为在胆甾醇水平未升高的 CTX 患者中可能会出现严重的神经系统受累。
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Clinical, biochemical, and molecular insights into Cerebrotendinous Xanthomatosis: A nationwide study of 100 Turkish individuals

Objective

Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder characterized by progressive neurologic and extraneurologic findings. The aim of this retrospective, descriptive study was to explore the time of presentation and diagnosis, and to expand the phenotype and genotype of CTX, based on a nationwide and comprehensive series of patients in Turkey.

Methods

The demographic, clinical, biochemical and genotypic characteristics of the CTX patients were reviewed. Data on molecular analysis, age of onset and diagnosis, diagnostic delay, neurologic and extraneurologic symptomatology, results of plasma cholestanol levels, brain magnetic resonance imaging and electromyography at the time of diagnosis were reviewed.

Results

100 confirmed CTX patients from 72 families were included. The mean age at diagnosis was 28.16 ± 14.28 years, and diagnostic delay was 18.39 ± 13.71 years. 36 patients were diagnosed in childhood. Frequency of intention tremor (p = 0.069), peripheral neuropathy (p = 0.234) and psychiatric manifestations (p = 0.396) did not differ between two groups, demonstrating the high rate in pediatric patients. Three adult patients showed a milder phenotype without neurologic involvement. Seven patients had normal plasma cholestanol levels despite neurological impairment. Sequencing of the CYP27A1 gene revealed 25 different variants, with a novel c.671_672del variant not previously described in literature.

Conclusion

Based on the observations of this Turkish CTX cohort, it is emphasized that the true prevalence of CTX is probably underestimated and that it has a wide spectrum of clinical phenotypes even without neurological impairment. In children, abnormal cerebellar findings, peripheral neuropathy and psychiatric findings associated with intellectual disability have been suggested as warning signs to avoid diagnostic delay. In cases of clinical suspicion, molecular analysis is recommended despite normal plasma cholestanol levels, as severe neurologic involvement may occur in CTX patients without elevated cholestanol levels.

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来源期刊
Molecular genetics and metabolism
Molecular genetics and metabolism 生物-生化与分子生物学
CiteScore
5.90
自引率
7.90%
发文量
621
审稿时长
34 days
期刊介绍: Molecular Genetics and Metabolism contributes to the understanding of the metabolic and molecular basis of disease. This peer reviewed journal publishes articles describing investigations that use the tools of biochemical genetics and molecular genetics for studies of normal and disease states in humans and animal models.
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