Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey
Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey
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DOI：
10.1111/j.1468-1331.2011.03439.x
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发表时间：
2011-10-01
影响因子：
5.1
通讯作者：
Sobrido, M. J.
中科院分区：
文献类型：
--
作者：
Pilo-de-la-Fuente, B.;Jimenez-Escrig, A.;Sobrido, M. J.
背景和目的：脑腱黄瘤病（CTX）是一种罕见的常染色体隐性遗传疾病，由CYP 27 A1基因突变引起的甾醇-27-羟化酶缺乏症。目前关于CTX的信息主要基于病例报告，只有少数大型系列报道。虽然被认为是一种潜在的可治疗的疾病，但鹅去氧胆酸加他汀类药物治疗的疗效仍不清楚。进行全国范围内的确诊病例调查，基因型-表型数据和预后factors.Methods的彻底分析：回顾性审查的临床和流行病学方面和突变的所有患者自1992年以来诊断的主要参考中心的CTX基因检测在Spains.Results：25例患者从19个家庭。从症状发作到临床诊断平均延迟19年。两个主要的临床亚组是可识别的：一个经典的形式（小脑和其他幕上症状）和脊柱形式（慢性脊髓病）。胆固醇水平与临床表现、严重程度或对治疗的反应无关。尽管接受了治疗，但仍有5名患者在诊断后1至4年的随访期间死亡。13个不同的突变被确定，与西班牙西北部和西班牙南部的p.R405W的p.R395C频率较高。没有一个突变可能与一个特定的临床特征组合或预后。结论：这是第一次全国范围内广泛的CTX系列报道在西班牙。某些地区的病例数较高，表明可能存在创始人效应。脊柱型预后不太严重。延迟诊断可能导致对治疗缺乏显著反应。
Background and purpose: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by mutations in the CYP27A1 gene resulting in sterol-27-hydroxylase deficiency. Current information about CTX is based mainly on case reports, with only few large series reported. Although perceived as a potentially treatable condition, efficacy of chenodeoxycholic acid plus statin therapy remains unclear. To perform a nationwide survey of confirmed cases, with a thorough analysis of genotype-phenotype data and prognostic factors.Methods: Retrospective review of the clinical and epidemiological aspects and mutations of all the patients diagnosed since 1992 in the main reference centers for genetic testing of CTX in Spain.Results: Twenty-five patients from 19 families were identified. An average delay of 19 years was observed between symptom onset and clinical diagnosis. Two main clinical subgroups were recognizable: a classic form (cerebellar and other supratentorial symptoms) and a spinal form (chronic myelopathy). Cholestanol levels did not correlate with clinical presentation, severity or response to therapy. Despite treatment, five patients died during follow-up, one to 4 years after diagnosis. Thirteen different mutations were identified, with a higher frequency of p.R395C in Northwestern Spain and p.R405W in Southern Spain. None of the mutations could be associated with a particular clinical feature combination or prognosis.Conclusions: This is the first nationwide extensive series of CTX reported in Spain. The higher number of cases in some areas suggests a possible founder effect. Spinal forms had a less severe prognosis. A delayed diagnosis could contribute to the lack of significant response to treatment.