Nishimura Samantha, Ma Charis, Sidransky Ellen, Ryan Emory
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Ther Clin Risk Manag. 2025 Jan 25;21:93-101. doi: 10.2147/TCRM.S388266. eCollection 2025.
Gaucher disease (GD) is a rare lysosomal storage disorder resulting from a deficiency of the lysosomal enzyme glucocerebrosidase caused by biallelic variants in the gene. Patients may present with a wide spectrum of disease manifestations, including hepatosplenomegaly, thrombocytopenia, bone manifestations, and in the case of GD types 2 and 3, neurodegeneration, cognitive delay, and/or oculomotor abnormalities. While there is no treatment for neuronopathic GD, non-neuronopathic manifestations can be efficiently managed with enzyme replacement therapy or substrate reduction therapy. However, many patients with GD experience a lengthy diagnostic odyssey, which can negatively affect their access to care and clinical outcomes. The cause of this diagnostic delay is multifaceted. Since genotype/phenotype correlations in GD are not always clear, it is difficult to predict the presence, severity, and onset of clinical manifestations. This heterogeneity, combined with the molecular complexity of the locus, low disease prevalence, and limited knowledge of GD among providers serves as a barrier to early diagnosis of GD. In this review, we discuss such obstacles and challenges, considerations, and future steps toward improving the diagnostic journey for patients with GD.
戈谢病（GD）是一种罕见的溶酶体贮积症，由该基因双等位基因变异导致溶酶体酶葡萄糖脑苷脂酶缺乏引起。患者可能出现广泛的疾病表现，包括肝脾肿大、血小板减少、骨骼表现，以及2型和3型戈谢病患者出现的神经退行性变、认知延迟和/或动眼神经异常。虽然目前尚无针对神经病变型戈谢病的治疗方法，但非神经病变型表现可通过酶替代疗法或底物减少疗法有效控制。然而，许多戈谢病患者经历漫长的诊断过程，这可能对他们获得治疗的机会和临床结局产生负面影响。这种诊断延迟的原因是多方面的。由于戈谢病的基因型/表型相关性并不总是明确的，因此很难预测临床表现的存在、严重程度和发病情况。这种异质性，再加上该基因座的分子复杂性、疾病低患病率以及医疗服务提供者对戈谢病的了解有限，成为戈谢病早期诊断的障碍。在本综述中，我们讨论了这些障碍和挑战、注意事项以及改善戈谢病患者诊断过程的未来步骤。
