Department of Pathology, Dutch Surveillance Centre for Prion Diseases, University Medical Centre Utrecht, GA Utrecht, The Netherlands.
J Neurol Neurosurg Psychiatry. 2010 Sep;81(9):1052-5. doi: 10.1136/jnnp.2009.175646. Epub 2010 Jun 14.
An atypical case of prion disease is described in a 54-year-old Dutch man, homozygous for valine at codon 129 of the prion protein gene (PRNP). The clinical phenotype was characterised by progressive dementia, spastic paraplegia and sensorimotor polyneuropathy. The disease duration was 20 months. Genetic analysis of PRNP did not reveal any abnormalities. Neuropathologically, only mild spongiform change and a coarse granular immunohistochemical staining for the abnormal prion protein, PrP(Sc), was observed, with poorly formed plaques in the molecular layer of the cerebellar cortex. However, Western blotting showed low but detectable levels of proteinase K(PK)-resistant PrP(Sc) occurring in an unusual ladder-like profile. These features define a phenotype that corresponds to the recently described protease-sensitive prionopathy (PSPr). Our report on the first Dutch patient with PSPr further expands the spectrum of prionopathies and exemplifies the need to re-evaluate cases of atypical prion disease.
本文报道了一例朊病毒病的不典型病例，患者为荷兰人，PRNP 基因第 129 密码子的缬氨酸为纯合子（valine at codon 129 of the prion protein gene [PRNP], homozygous）。临床表现为进行性痴呆、痉挛性截瘫和感觉运动性多发性神经病。病程为 20 个月。PRNP 的基因分析未发现任何异常。神经病理学检查仅发现轻度海绵状改变和异常朊病毒蛋白（PrP(Sc)）的粗糙颗粒状免疫组织化学染色，小脑皮质分子层有形成不良的斑块。然而，Western blot 显示，蛋白水解酶（proteinase K [PK]）抗性 PrP(Sc)水平较低，但可检测到，呈异常梯状图谱。这些特征定义了一种与最近描述的蛋白酶敏感朊病毒病（protease-sensitive prionopathy [PSPr]）相符的表型。本报告为首例荷兰 PSPr 患者，进一步扩展了朊病毒病的谱，并说明了需要重新评估不典型朊病毒病病例的必要性。
