Mignarri Andrea, Gallus Gian Nicola, Dotti Maria Teresa, Federico Antonio
Unit of Neurology and Neurometabolic Disorders, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100, Siena, Italy.
J Inherit Metab Dis. 2014 May;37(3):421-9. doi: 10.1007/s10545-013-9674-3. Epub 2014 Jan 18.
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder characterized by a heterogeneous presentation and a broad spectrum of clinical manifestations. Since early diagnosis and replacement therapy with chenodeoxycholic acid can prevent clinical deterioration, our aim was to develop a diagnostic tool to identify and treat CTX patients at an initial stage of the disease.
We devised a suspicion index, composed of weighted scores assigned to indicators such as family history characteristics and common systemic and neurological features, on the basis of a pooled analysis of selected international CTX series. The indicators were classified as very strong (score 100), strong (50) or moderate (25). The suspicion index was then applied retrospectively to our CTX population.
Early systemic signs such as cataract, diarrhea and neonatal cholestatic jaundice were considered strong indicators, together with neurological features such as intellectual impairment, psychiatric disturbances, ataxia, spastic paraparesis and dentate nuclei abnormalities at MRI. Tendon xanthomas were regarded as very strong indicators, as was an affected sibling. A total score ≥ 100 warranted serum cholestanol assessment. Elevated cholestanol or a total score ≥ 200, with one very strong or four strong indicators, warranted CYP27A1 gene analysis. In our patients, age at diagnosis was 35.5 ± 11.8 years (mean ± standard deviation), whereas with the diagnostic tool it became 10.6 ± 9.8 years (p < 0.01).
Our suspicion index provides a simple and inexpensive diagnostic tool allowing diagnosis and treatment of CTX before neurological disability occurs.
脑腱黄瘤病（CTX）是一种常染色体隐性脂质贮积病，其表现具有异质性，临床表现范围广泛。由于早期诊断并用鹅去氧胆酸进行替代治疗可防止临床病情恶化，我们的目标是开发一种诊断工具，以便在疾病的初始阶段识别和治疗CTX患者。
我们在对选定的国际CTX系列进行汇总分析的基础上，设计了一个怀疑指数，该指数由赋予诸如家族史特征以及常见的全身和神经特征等指标的加权分数组成。这些指标被分类为非常强（分数100）、强（50）或中等（25）。然后将该怀疑指数回顾性应用于我们的CTX患者群体。
早期的全身症状如白内障、腹泻和新生儿胆汁淤积性黄疸被视为强指标，还有神经特征如智力障碍、精神障碍、共济失调、痉挛性截瘫以及MRI显示的齿状核异常。肌腱黄瘤被视为非常强的指标，患病的同胞也是。总分≥100时需要进行血清胆甾烷醇评估。胆甾烷醇升高或总分≥200，且有一个非常强的指标或四个强指标时，需要进行CYP27A1基因分析。在我们的患者中，诊断时的年龄为35.5±11.8岁（平均值±标准差），而使用该诊断工具后变为10.6±9.8岁（p<0.01）。
我们的怀疑指数提供了一种简单且经济的诊断工具，能够在神经功能残疾出现之前对CTX进行诊断和治疗。
