Svarstad Einar, Leh Sabine, Skrunes Rannveig, Kampevold Larsen Kristin, Eikrem Øystein, Tøndel Camilla
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Nephron. 2018;138(1):13-21. doi: 10.1159/000479751. Epub 2017 Aug 26.
BACKGROUND/AIMS: A previous case report found stereomicroscopic changes typical for Fabry disease in a kidney biopsy. This case series evaluates an expanded diagnostic capacity of the method.
Bedside stereomicroscopy was performed in a cross-sectional prospective study of 31 consecutive enzyme-treated or treatment-naïve male (n = 14) and female Fabry disease patients. The burden of glomerular storage material was scored semiquantitatively on a visual analog scale (range 0-3) and a blinded comparison was done with a reference histologic method.
Significant correlations (p < 0.001) were found between the stereomicroscopic scoring of glomerular characteristic white storage material and the amount of podocyte globotriaosylceramide (Gb3) deposits scored by standardized light microscopy. The bedside method correctly identified the variability of podocyte Gb3 accumulation after 10 years of identical agalsidase therapy in 2 brothers aged 24 and 27 years, and also identified tubular cell deposits. Stereomicroscopy correctly verified the absence of sphingolipid deposits in the biopsy of a female index patient with a genetic variant of unknown significance, and the diagnosis of Fabry disease was finally discarded.
Bedside stereomicroscopy of kidney biopsies is an easily available, low-cost microscopy method handled by the clinician. The method carries a high diagnostic sensitivity for Fabry disease, reducing the risk of misdiagnosis in previously unknown cases. An expanded yield of the method is suggested, including the grading of the podocyte Gb3 burden and assessment of effectiveness of enzyme replacement therapy. We recommend the method as complementary to current standard histologic evaluation of Fabry kidney biopsies.
背景/目的：先前的一份病例报告在肾活检中发现了法布里病典型的立体显微镜变化。本病例系列评估了该方法扩大后的诊断能力。
对31例连续接受酶治疗或未接受治疗的男性（n = 14）和女性法布里病患者进行了横断面前瞻性研究，采用床边立体显微镜检查。肾小球储存物质的负荷在视觉模拟量表（范围0 - 3）上进行半定量评分，并与参考组织学方法进行盲法比较。
肾小球特征性白色储存物质的立体显微镜评分与标准化光学显微镜下足细胞神经酰胺三己糖苷（Gb3）沉积量之间存在显著相关性（p < 0.001）。床边方法正确识别了24岁和27岁的两兄弟在接受10年相同的阿加糖酶治疗后足细胞Gb3积累的变异性，还识别出了肾小管细胞沉积。立体显微镜正确验证了一名具有意义不明基因变异的女性索引患者活检中鞘脂沉积的缺失，最终排除了法布里病的诊断。
肾活检的床边立体显微镜检查是一种临床医生易于使用、低成本的显微镜检查方法。该方法对法布里病具有较高的诊断敏感性，降低了既往未知病例误诊的风险。建议扩大该方法的应用范围，包括对足细胞Gb3负荷进行分级以及评估酶替代治疗的有效性。我们建议将该方法作为法布里肾活检当前标准组织学评估的补充方法。
