一例以精神发育迟滞起病的脑腱黄瘤病的病例分析

Analysis of a cerebrotendinous xanthomatosis case with mental retardation as the initial symptom

目的对1例以精神发育迟滞（mentalretardation，MR）为神经系统首发症状的脑腱黄瘤病（cerebrotendinousxanthomatosis，CTx）进行分析。方法综合应用影像学检查、组织病理检测及基因检测对患者进行分析。结果患者为男性，27岁，具有典型的神经系统症状，先后出现MR、记忆力减退、共济失调、痉挛性截瘫、言语呐呓等。非神经系统症状有白内障、双跟腱肿物、肾结石和高弓足等。血清总胆汁酸升高（14．7μmol／L）。头部磁共振扫描示双侧小脑齿状核对称性T1WI和DWI呈低信号，T2WI呈混杂信号；双侧脑室旁异常信号。跟腱组织光镜下可见胆固醇结晶，胆固醇肉芽肿性炎症。CYP27Al基因第2外显子检出P．Argl27Trp（C．379CT）杂合变异，第6外显子检出P．Glu392I．ys（C．1174G〉A）杂合突变。结论青少年出现由遗传代谢因素导致的MR并伴随肌腱黄瘤和白内障等时，应高度怀疑脑腱黄瘤病。可通过组织病理、CyP27Aj基因检测明确诊断。

Objective To analyze a case of cerebrotendinous xanthomatosis （CTX） with mental retardation as the initial neurological symptom. Methods Medical imaging, histopathological assay and genetic testing were carried out to analyze the patient. Results Neurological manifestations of the 27-year-old male patient were initiated by mental retardation and subsequently memory lapses, ataxia, spastic paraplegia and fuzzy language. Other symptoms included cataract, xanthomatosis in Achilles tendon, kidney stones and high arches. The total bile acid in serum has risen to 14.7 μmol/L. There were symmetrical abnormal signals in bilateral cerebellar dentate nuclei, hypointensities on TlWI and DWI and mixed signals on T2WI. Cholesterol crystallization and cholesterol granulomatous inflammation were found upon pathological examination of the Achilles tendon. The patient was found to have carried a compound heterozygous mutation of the CTX gene, which consisted of two novel mutations including c. 379CT （p. Arg127Trp） in exon 2 and c. 1174G〉A （p. Glu392Lys） in exon 6 of the CYP27A1 gene. Conclusion Clinicians should be alert to cerebrotendinous xanthomatosis when the patient has mental retardation caused by genetic and metabolic factors beginning at a young age, particularly accompanied with tendinous xanthomatosis and cataracts. CTX can be readily diagnosed by histopathological assay and sequencing of the CYP27A1 gene.