Primary ciliary dyskinesia: critical evaluation of clinical symptoms and diagnosis in patients with normal and abnormal ultrastructure

Orphanet Journal of Rare Diseases

Kris De Boeck⁷  Mark Jorissen³  Veronique Godding⁴  Anne Malfroot²  Sabine Van Daele¹  Francois L Vermeulen⁷  Lieven J Dupont⁶  Marijke Proesmans⁷  Martine Jaspers³  Harry Cuppens⁵  Anne Smits⁷  Mieke Boon⁷ 

[1] Department of Pediatrics, Pediatric Pulmonology, University Hospital Ghent, Ghent, Belgium;Department of Pediatrics, Pediatric Pulmonology, Universitair Ziekenhuis Brussel UZB, Brussel, Belgium;Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leuven, Leuven, Belgium;Department of Pediatrics, Pneumologie Pédiatrique et Mucoviscidose, UCL St-Luc, Brussels, Belgium;Center for Human Genetics, KUL, Leuven, Belgium;Department of Pulmonology, University Hospital Leuven, Leuven, Belgium;Department of Pediatrics, Pediatric Pulmonology, University Hospital Leuven, Leuven, Belgium

关键词: DNAH11;    Transmission electron microscopy;    Primary ciliary dyskinesia;    Population characteristics;    Ultrastructure;    Primary cell culture;   

Others  :  863272
DOI  :  10.1186/1750-1172-9-11

 received in 2013-08-27, accepted in 2014-01-15,  发布年份 2014

【 摘 要 】

Background

Primary ciliary dyskinesia (PCD) is a rare disorder with variable disease progression. To date, mutations in more than 20 different genes have been found. At present, PCD subtypes are described according to the ultrastructural defect on transmission electron microscopy (TEM) of the motile cilia. PCD with normal ultrastructure (NU) is rarely reported because it requires additional testing. Biallelic mutations in DNAH11 have been described as one cause of PCD with NU.

The aim of our study was to describe the clinical characteristics of a large population of patients with PCD, in relation to the ultrastructural defect. Additionally, we aimed to demonstrate the need for biopsy and cell culture to reliably diagnose PCD, especially the NU subtype.

Methods

We retrospectively analyzed data from 206 patients with PCD. We compared the clinical characteristics, lung function, microbiology and imaging results of 68 patients with PCD and NU to those of 90 patients with dynein deficiencies and 41 patients with central pair abnormalities. In addition, we aimed to demonstrate the robustness of the diagnosis of the NU subtype in cell culture by data from genetic analysis.

Results

PCD with NU comprised 33% (68/206) of all patients with PCD. Compared to other subtypes, patients with PCD and NU had a similar frequency of upper and lower respiratory tract problems, as well as similar lung function and imaging. With the currently widely applied approach, without cell culture, the diagnosis would have been missed in 16% (11/68) of patients with NU. Genetic analysis was performed in 29/68 patients with PCD and NU, and biallelic mutations were found in 79% (23/29) of tested patients.

Conclusions

We reported on the clinical characteristics of a large population of patients with PCD and NU. We have shown that systematic performance of biopsy and cell culture increases sensitivity to detect PCD, especially the subtype with NU.

PCD with NU has similar clinical characteristics as other PCD types and requires biopsy plus ciliogenesis in culture for optimal diagnostic yield.

【 授权许可】

   
2014 Boon et al.; licensee BioMed Central Ltd.

【 图 表 】

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