Rocchetti Maria Teresa, Spadaccino Federica, Catalano Valeria, Zaza Gianluigi, Stallone Giovanni, Fiocco Daniela, Netti Giuseppe Stefano, Ranieri Elena
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
Unit of Clinical Pathology, Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
Metabolites. 2022 Jul 28;12(8):703. doi: 10.3390/metabo12080703.
Fabry disease (FD) is an X-linked lysosomal disease due to a deficiency in the activity of the lysosomal-galactosidase A (GalA), a key enzyme in the glycosphingolipid degradation pathway. FD is a complex disease with a poor genotype-phenotype correlation. In the early stages, FD could involve the peripheral nervous system (acroparesthesias and dysautonomia) and the ski (angiokeratoma), but later kidney, heart or central nervous system impairment may significantly decrease life expectancy. The advent of omics technologies offers the possibility of a global, integrated and systemic approach well-suited for the exploration of this complex disease. In this narrative review, we will focus on the main metabolomic studies, which have underscored the importance of detecting biomarkers for a diagnostic and prognostic purpose in FD. These investigations are potentially useful to explain the wide clinical, biochemical and molecular heterogeneity found in FD patients. Moreover, the quantitative mass spectrometry methods developed to evaluate concentrations of these biomarkers in urine and plasma will be described. Finally, the complex metabolic biomarker profile depicted in FD patients will be reported, which varies according to gender, types of mutations, and therapeutic treatment.
法布里病（FD）是一种X连锁溶酶体疾病，由于溶酶体半乳糖苷酶A（GalA）活性缺乏所致，GalA是糖鞘脂降解途径中的关键酶。FD是一种复杂疾病，基因型与表型的相关性较差。在疾病早期，FD可累及周围神经系统（肢端感觉异常和自主神经功能障碍）和皮肤（血管角质瘤），但后期肾脏、心脏或中枢神经系统损害可能会显著缩短预期寿命。组学技术的出现为全面、综合和系统地研究这种复杂疾病提供了可能。在这篇叙述性综述中，我们将重点关注主要的代谢组学研究，这些研究强调了检测生物标志物对于FD诊断和预后的重要性。这些研究可能有助于解释FD患者中广泛存在的临床、生化和分子异质性。此外，还将描述为评估尿液和血浆中这些生物标志物浓度而开发的定量质谱方法。最后，将报告FD患者呈现的复杂代谢生物标志物谱，其会因性别、突变类型和治疗方法而有所不同。
