Abstract
Introduction: The presence of ultrastructural abnormalities (UA) on transmission electron microscopy (TEM) is proposed as gold standard for the diagnosis of Primary Ciliary Dyskinesia (PCD). Functional evaluation after ciliogenesis in culture (CC) is only proposed if the diagnosis is doubted. Because secondary changes are frequent, all samples are evaluated by CC at our centre. Since the detection of a DNAH11 mutation, the existence of the subtype normal ultrastructure but abnormal motility (NU) is proven. Using CC, we show that this subtype is not as rare as thought.
Methods: Over 22 years, the CC procedure was used in 3077 subjects, of which 200 were diagnosed as PCD. Epithelial cells are isolated from nasal biopsies and cultured as a monolayer. After losing all the cilia they are brought into suspension, to gain cilia de novo.
Results: UA was found in 133 subjects, NU in 67. In only 35 of the NU, ciliary beat frequency (CBF) could be measured before CC. It was abnormal in 22 and normal in 13, with absent ciliary coordination in 7 of these 13. After CC, all the samples lacked coordination, pathognomonic for PCD. CBF was abnormal in 50 and normal in 17 subjects. Repeat biopsy in 18 patients was identical. CC was the only technique to make the diagnosis of PCD in 39 subjects.
nNO did not significantly differ from the UA group. There was familial occurrence of NU in 4 sibling pairs, consanguinity in 13.6%, situs inversus in 34%. The clinical characteristics (bronchiectasis, nasal secretions, hearing loss, draining ears, polyposis nasi, infertility) were similar in UA and NA.
Conclusion: CC is the most reliable tool to diagnose PCD and unambigouosly detect patients with PCD and NA who might be missed when using other diagnostic methods.
- © 2012 ERS
