Diagnostik und Therapie der primären ziliären Dyskinesie

Zusammenfassung

Die primäre ziliäre Dyskinesie (PCD) ist eine klinisch und genetisch heterogene hereditäre Erkrankung. Der komplexe Phänotyp der Erkrankung erklärt sich durch angeborene Dysfunktionen respiratorischer Flimmerhärchen (Zilien), embryonaler Zilien und von Spermienschwänzen. Aufgrund einer verminderten mukoziliären Reinigung der Atemwege entwickeln Betroffene rezidivierende Infektionen der oberen und unteren Atemwege. Embryonale Ziliendefekte sind dafür verantwortlich, dass die Hälfte der PCD-Patienten einen Situs inversus (Kartagener-Syndrom) aufgrund einer zufälligen Anordnung der Links/Rechts-Körperasymmetrie aufweist. Bei betroffenen Männern verursacht eine Fehlfunktion der Spermienschwänze oft eine verminderte Fertilität (∼60%). Bei klinischem Verdacht kann die Diagnose durch Elektronenmikroskopie, hoch auflösende Immunfluoreszenzmikroskopie, und/oder direktmikroskopische Evaluation des Zilienschlages bestätigt werden. Kürzlich konnten Mutationen bei rezessiv vererbter PCD in den Genen DNAI1, DNAH5, DNAH11 nachgewiesen werden. Selten finden sich RPGR-Mutationen bei Jungen mit X-chromosomal rezessiver PCD und Retinitis pigmentosa. Das aktuelle therapeutische Konzept wird vorgestellt.

Summary

Primary ciliary dyskinesia (PCD) is a phenotypically and genetically heterogeneous genetic disorder. The disease phenotype results from defects of respiratory cilia, sperm tails and the cilia of the embryonic node. Recurrent infections of the upper and lower airways are caused defective mucociliary clearance. Early diagnosis is important prevent or delay permanent lung damage (bronchiectasis) that might even progress to chronic respiratory failure. Male infertility due to sperm tail dysmotility is often observed. Randomization of left/right body asymmetry is responsible for situs inversus (Kartagener’s syndrome) in half of affected individuals. As a screening test nasal nitric oxide measurement is used, but only available in few specialized centers. Establishment of diagnosis currently relies on electron microscopy, high-resolution immunofluorescence analysis, and/or direct evaluation of ciliary beat by light microscopy. Recently mutations in the three genes DNAI1, DNAH5 and DNAH11 that all encode for dynein proteins have been linked to recessive PCD. In addition mutations in the RPGR gene located on the X chromosome have been identified in males with retinitis pigmentosa and PCD.

Schlüsselwörter

Primäre ziliäre Dyskinesie - Dysmotilität der Flimmerhärchen - Dyneinproteine

Keywords

Primary ciliary dyskinesia - Dyskinesia of cilia - dynein proteins

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