The impact of guideline implementation in diagnosing primary ciliary dyskinesia using transmission electron microscopy

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterised by dysfunctional motile cilia. Although diagnostic guidelines recommend transmission electron microscopy (TEM) as one of the confirmatory methods, inconsistent reporting practices have posed significant challenges. We evaluated the impact of implementing the International consensus guidelines for reporting TEM results in diagnosing PCD. We compared TEM results of nasal/bronchial biopsy samples from 16 children and adolescents with confirmed or suspected PCD, before and after guideline implementation, alongside genetic testing. Prior to the guidelines, TEM informed suspicion of PCD in 4 out of 16 patients (25%), but no hallmark defects were described. After guideline implementation, PCD was diagnosed in 11 cases (69%), with class 1 hallmark defects in 9 cases and class 2 defects in 2 cases. The results were inconclusive in 6% (n=1), with secondary changes in 6% (n=1) and reclassified as insufficient sample in 19% (n=3) of subjects. Genetic tests from 9 out of the 11 diagnosed cases correlated with the expected ultrastructural defects; in the remaining 2 cases, the TEM defect was described as ODA + IDA, yet the genetic variants found were associated with ODA defects. DRC1 variants in homozygous and single variant forms were identified in patients with secondary changes and inconclusive TEM results. Our study shows that implementing the International consensus guidelines for reporting TEM results significantly enhances the diagnostic yield in PCD cases. Standardised reporting criteria that emphasise hallmark abnormalities can improve the sensitivity and specificity of PCD diagnosis.