Ultrastructure for the diagnosis of primary ciliary dyskinesia in South Africa, a resource-limited setting

Abstract

IntroductionInternational guidelines recommend a multi-faceted approach for successful diagnoses of primary ciliary dyskinesia (PCD). In the absence of a gold standard test, a combination of genetic testing/microscopic analysis of structure and function/nasal nitric oxide measurement is used. In resource-limited settings, often none of the above tests are available, and in South Africa, only transmission electron microscopy (TEM) is available in central anatomical pathology departments. The aim of this study was to describe the clinical and ultrastructural findings of suspected PCD cases managed by pediatric pulmonologists at a tertiary-level state funded hospital in Johannesburg.MethodsNasal brushings were taken from 14 children with chronic respiratory symptoms in keeping with a PCD phenotype. Ultrastructural analysis in accordance with the international consensus guidelines for TEM-PCD diagnostic reporting was undertaken.ResultsTEM observations confirmed 43% (6) of the clinically-suspected cases (hallmark ultrastructural defects in the dynein arms of the outer doublets), whilst 57% (8) required another PCD testing modality to support ultrastructural observations. Of these, 25% (2) had neither ultrastructural defects nor did they present with bronchiectasis. Of the remaining cases, 83% (5) had very few ciliated cells (all of which were sparsely ciliated), together with goblet cell hyperplasia. There was the apparent absence of ciliary rootlets in 17% (1) case.DiscussionIn resource-limited settings in which TEM is the only available testing modality, confirmatory and probable diagnoses of PCD can be made to facilitate early initiation of treatment of children with chronic respiratory symptoms.

Primary Ciliary Dyskinesia: A Clinical Review

“…Abbreviations: a TEM = transmission electron microscopy; b nNO = nasal nitric oxide, with <77 nL/min abnormal; c ODA = outer dynein arm; d NR = not reported; e IDA = inner dynein arm; f MTD = microtubular disorganization. 1 . Hypomorphic variant results in variable EM phenotypes.…”

“…As many as 40% of biopsies may have inadequate cilia for analysis by TEM [ 134 , 143 , 144 ]. Moreover, TEM evaluations require considerable experience and expertise, though recent international guidelines for TEM interpretation have helped [ 1 , 103 ]. Additional techniques such as cryotomography or image processing may help further clarify structures for analysis but are still largely experimental [ 145 , 146 ].…”

“…Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, motile ciliopathy characterized by ineffective ciliary movement leading to recurrent upper and lower respiratory tract infections, neonatal respiratory distress, subfertility, and laterality defects. “Primary” indicates a genetic or inherited cause of ciliary dysfunction, distinct from “secondary” or acquired causes of ciliary dysfunction, typically related to epithelial injury in the airway from insults including infections and pollution [ 1 ]. Population estimates of the prevalence of PCD have ranged from 1:10,000 to 1:30,000, though these values are likely underestimates due to under-recognition and difficulty in diagnosing this condition [ 2 , 3 , 4 , 5 ].…”