Diagnosis of primary ciliary dyskinesia: potential options for resource-limited countries

Abstract

Primary ciliary dyskinesia is a genetic disease of ciliary function leading to chronic upper and lower respiratory tract symptoms. The diagnosis is frequently overlooked because the symptoms are nonspecific and the knowledge about the disease in the primary care setting is poor. Additionally, none of the available tests is accurate enough to be used in isolation. These tests are expensive, and need sophisticated equipment and expertise to analyse and interpret results; diagnosis is therefore only available at highly specialised centres. The diagnosis is particularly challenging in countries with limited resources due to the lack of such costly equipment and expertise.In this review, we discuss the importance of early and accurate diagnosis especially for countries where the disease is clinically prevalent but diagnostic tests are lacking. We review the diagnostic tests available in specialised centres (nasal nitric oxide, high-speed video microscopy, transmission electron microscopy, immunofluorescence and genetics). We then consider modifications that might be considered in less well-resourced countries whilst maintaining acceptable accuracy.

FIGURE 1

Transmission electron micrographs of human airway cilia in transverse section of a) normal subjects, and examples of hallmark defects depicting b) the absence of outer dynein arms, c) the combined absence of inner and outer dynein arms, and d) inner arm absence combined with microtubular disarrangement. Scale bar=200 nm.

FIGURE 2

Fluorescence confocal micrograph images of human ciliated nasal epithelial cells showing presence (normal) or absence (examples here from different primary ciliary dyskinesia (PCD) patients) of ciliary proteins by labelling with antibodies against DNALI1 (inner dynein arm), DNAH5 (outer dynein arm) and RSPH4A (radial spoke head) in red. β-tubulin was used as a consistent cilium marker (green) and cell nuclei were counterstained with DAPI (blue). Scale bar=40 μm.