Zedde Marialuisa, Pascarella Rosario, Cavallieri Francesco, Pezzella Francesca Romana, Grisanti Sara, Di Fonzo Alessio, Valzania Franco
Neurology Unit, Neuromotor and Rehabilitation Department, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
Neuroradiology Unit, Radiology Department, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.
Biomedicines. 2022 Dec 5;10(12):3132. doi: 10.3390/biomedicines10123132.
Anderson-Fabry disease (AFD) is an inherited lysosomal storage disorder characterized by a composite and multisystemic clinical phenotype and frequent involvement of the central nervous system (CNS). Research in this area has largely focused on the cerebrovascular manifestations of the disease, and very little has been described about further neurological manifestations, which are known in other lysosomal diseases, such as Gaucher disease. In particular, a clinical and neuroimaging phenotype suggesting neurodegeneration as a putative mechanism has never been fully described for AFD, but the increased survival of affected patients with early diagnosis and the possibility of treatment have given rise to some isolated reports in the literature on the association of AFD with a clinical phenotype of Parkinson disease (PD). The data are currently scarce, but it is possible to hypothesize the molecular mechanisms of cell damage that support this association; this topic is worthy of further study in particular in relation to the therapeutic possibilities, which have significantly modified the natural history of the disease but which are not specifically dedicated to the CNS. In this review, the molecular mechanisms underlying this association will be proposed, and the available data with implications for future research and treatment will be rewritten.
安德森-法布里病(AFD)是一种遗传性溶酶体贮积症,其特征为复杂的多系统临床表型,且中枢神经系统(CNS)常受累。该领域的研究主要集中在该病的脑血管表现,而对于其他溶酶体疾病(如戈谢病)中已知的进一步神经学表现则描述甚少。特别是,尚未对提示神经退行性变作为一种假定机制的临床和神经影像学表型进行全面描述,但随着早期诊断后受影响患者生存率的提高以及治疗的可能性,文献中出现了一些关于AFD与帕金森病(PD)临床表型关联的孤立报道。目前数据稀少,但有可能推测支持这种关联的细胞损伤分子机制;这个主题尤其值得进一步研究,特别是关于治疗可能性,治疗已显著改变了该病的自然史,但并非专门针对中枢神经系统。在这篇综述中,将提出这种关联背后的分子机制,并重新梳理对未来研究和治疗有影响的现有数据。