目的:脑性黄瘤病(CTX)是一种遗传性代谢疾病,其特征是进行性神经和神经外表现。这次回顾的目的,描述性研究是探索呈现和诊断的时间,扩大CTX的表型和基因型,基于土耳其全国范围内的全面患者系列。
方法:人口统计,临床,对CTX患者的生化和基因型特征进行了回顾。分子分析数据,发病和诊断年龄,诊断延迟,神经和神经外症状学,血浆胆固醇水平的结果,对诊断时的脑磁共振成像和肌电图进行了回顾。
结果:包括来自72个家庭的100例确诊的CTX患者。诊断时的平均年龄为28.16±14.28岁,诊断延迟为18.39±13.71年。36例患者在儿童期被诊断。故意震颤的频率(p=0.069),两组间周围神经病变(p=0.234)和精神病表现(p=0.396)无差异,证明儿科患者的发病率很高。三名成年患者表现出轻度表型,没有神经系统受累。尽管神经功能缺损,但7例患者的血浆胆固醇水平正常。CYP27A1基因的测序揭示了25种不同的变异,具有先前文献中未描述的新型c.671_672del变体。
结论:根据土耳其CTX队列的观察,需要强调的是,CTX的真实患病率可能被低估了,即使没有神经功能缺损,它也具有广泛的临床表型.在儿童中,小脑异常发现,与智力障碍相关的周围神经病变和精神病表现被认为是避免诊断延迟的警告信号.在临床怀疑的情况下,尽管血浆胆固醇水平正常,但仍建议进行分子分析,因为在未升高胆固醇水平的CTX患者中可能发生严重的神经系统受累。
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.
CONCLUSIONS: 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.