Abstract：
There are few cerebrotendineous xanthomatosis (CTX) case series and observational studies including a significant number of Latin American patients. We describe a multicenter Brazilian cohort of patients with CTX highlighting their clinical phenotype, recurrent variants and assessing possible genotype-phenotype correlations. We analyzed data from all patients with clinical and molecular or biochemical diagnosis of CTX regularly followed at six genetics reference centers in Brazil between March 2020 and August 2023. We evaluated 38 CTX patients from 26 families, originating from 4 different geographical regions in Brazil. Genetic analysis identified 13 variants in the CYP27A1 gene within our population, including 3 variants that had not been previously described. The most frequent initial symptom of CTX in Brazil was cataract (27%), followed by xanthomas (24%), chronic diarrhea (13.5%), and developmental delay (13.5%). We observed that the median age at loss of ambulation correlates with the age of onset of neurological symptoms, with an average interval of 10 years (interquartile range 6.9 to 11 years). This study represents the largest CTX case series ever reported in South America. We describe phenotypic characteristics and report three new pathogenic or likely pathogenic variants.
摘要：
很少有脑性黄瘤病（CTX）病例系列和观察性研究，包括大量拉丁美洲患者。我们描述了一个巴西CTX患者的多中心队列，突出了他们的临床表型，复发性变异和评估可能的基因型-表型相关性。我们分析了2020年3月至2023年8月在巴西六个遗传学参考中心定期随访的所有CTX临床和分子或生化诊断患者的数据。我们评估了来自26个家庭的38名CTX患者，原产于巴西4个不同的地理区域。遗传分析确定了我们人群中CYP27A1基因的13个变异，包括3个以前没有描述过的变种.在巴西，CTX最常见的初始症状是白内障（27％），其次是黄色瘤（24%），慢性腹泻（13.5%），和发育迟缓(13.5%)。我们观察到，步行失败的中位年龄与神经系统症状发作的年龄相关，平均间隔为10年（四分位数间隔6.9至11年）。这项研究代表了南美有史以来最大的CTX病例系列。我们描述了表型特征，并报告了三种新的致病性或可能的致病性变异。
