Targeted urine microscopy in Anderson-Fabry Disease: a cheap, sensitive and specific diagnostic technique

Abstract

We investigate the use of wetting films to significantly improve the imaging performance of lensfree pixel super-resolution on-chip microscopy, achieving < 1 µm spatial resolution over a large imaging area of ~24 mm 2. Formation of an ultra-thin wetting film over the specimen effectively creates a micro-lens effect over each object, which significantly improves the signal-to-noise-ratio and therefore the resolution of our lensfree images. We validate the performance of this approach through lensfree on-chip imaging of various objects having fine morphological features (with dimensions of e.g., ≤0.5 µm) such as Escherichia coli (E. coli), human sperm, Giardia lamblia trophozoites, polystyrene micro beads as well as red blood cells. These results are especially important for the development of highly sensitive field-portable microscopic analysis tools for resource limited settings., "Two-dimensional standing wave total internal reflection fluorescence microscopy: superresolution imaging of single molecular and biological specimens," Biophys. J.

Lipiduria – with special relevance to Fabry disease

“…By this technique we were able to identify GL3 in renal podocytes in patients Fabry urine [17]. We suggest that using the examination of urinary sediment with polarised light microscopy may be a useful way to detect Fabry disease particularly in situations where enzyme or genetic analysis is unavailable.…”

“…We therefore asked the question "can urine microscopy help, across a wide phenotypic spectrum?" [17].…”

Fabry Nephropathy: An Evidence-Based Narrative Review

“…3) Urine microscopy has demonstrated usefulness in diagnosing FD, as vacuolated epithelial cells, filled with glycosphingolipids, giving the appearance of a 'Maltese cross', can be seen using polarized light microscopy [56]. One report has suggested that screening for mulberry cells (regarded as distal tubular epithelial cells in which Gb3 has accumulated) during urinalysis could be a simple, inexpensive, and non-invasive method for diagnosing this Fabry nephropathy in the absence of proteinuria [57].…”

Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

“…Genotyping can also be useful in male patients to assist with tracing family history of the disease. Urine microscopy may be clinically useful in diagnosing Fabry disease: vacuolated epithelial cells, filled with glycosphingolipids, giving the appearance of a ‘Maltese cross’, can be seen using polarized light microscopy [31]. Assessment of renal Fabry disease involves several assessments and tools (Table 1), with renal biopsy being particularly important to assess and monitor disease progression long term [32].…”