脑腱性黄色瘤病的临床特征与基因突变分析

Clinical characteristics and gene mutation analysis of cerebrotendinous xanthomatosis

目的分析脑腱性黄色瘤病（cerebrotendinous xanthomatosis，CTX）的临床表现、实验室检查特点、影像学特征及甾醇-27羟化酶基因（CYP27A1）突变，旨在提高对此病的认识，以利早期诊断和治疗。方法对1例临床诊断为CTX的家系行CYP27A1基因突变分析，收集先证者的临床资料，进行为期8个月的随访，并结合文献对CTX的疾病特征进行分析。结果患者为36岁男性，神经系统损害主要表现为智能低下，双侧皮质脊髓束、皮质脑干束受损表现，以及小脑及周围神经病变的表现；头颅MRI提示双侧基底节对称异常信号，小脑齿状核软化及钙化灶；跟腱MRI提示跟腱显著增粗；基因突变分析发现先证者存在CYP27A1基因5号外显子第1016位核苷酸C→T纯合突变，而先证者母亲与姐姐分别存在该基因第1016位核苷酸C→T杂合突变，为携带者。先证者予熊去氧胆酸治疗，随访8个月，患者前6个月规律服药，病情稳定，近2个月自行停药，病情加重。结论CYP27A1基因5号外显子第1016位核苷酸存在C→T纯合突变（p．T339M）导致该患者发生CTX，符合常染色体隐性遗传特点。CTX临床表现具有一定的特征性，如跟腱增粗、智能减退、共济失调等，但早期影像学检查缺乏特异性，易被延误诊治。CYP27A1基因突变检测对早期诊断CTX具有重要意义，应予以重视，而早期应用鹅去氧胆酸治疗能延缓疾病进展。

Objective To investigate the clinical presentation, laboratory features, imaging findings and CYP27A1 gene mutations of cerebrotendinous xanthomatosis （CTX） for improving the recognition and the early diagnosis and treatment of the disease. Methods Medical records and 8 months follow-up data of one patient who had been clinical diagnosed as CTX were collected and the pedigree and gene mutation analysis of the patient were carried out. Meanwhile, the clinical characters of CTX were analyzed according to the data from our patient and the review of the literature. Results Patient was a 36 years old male manifested with mental retardation, bilateral corticospinal tract and corticonuclear tract impairment, cerebellar lesions and peripheral neuropathy; head MRI indicated symmetric abnormal signals of bilateral basal ganglia, cerebellar dentate nucleus softening and calcification lesions; Achilles tendon MRI indicated markedly thickened Achilles tendon; gene mutation analysis showed sterol-27-hydroxylase gene（ CPY27A1 ） C→T homozygous mutation in 1016 nucleotide of exon 5. Ursodesoxycholic acid was given as treatment. In 8 months of follow up, for the first 6 months, the patient took medicine regularly and the illness condition was stable. But for the nearly 2 months, the patient voluntarily stopped medicine and the illness condition was worse. Conclusions CPY27A1 gene C→T homozygous mutation in 1016 nucleotide of exon 5 leads to CTX in the patient, which conforms to the characteristic of autosomal recessive disorder. CTX has some characteristic clinical manifestations, such as Achilles tendon thickening, intelligent declining and so on. But lack of specificity of early radiographic examination makes CTX easy to be delayed diagnosis and treatment. CYP27A1 gene mutation analysis has an important significance for early diagnosis of CTX, which should be paid more attention, while the early application of chenodeoxycholicacid treatment can delay the progression of the disease.