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Diagnostik der primären ziliären Dyskinesie

Empfehlungen in Zusammenarbeit mit Kartagener-Syndrom und Primäre Ciliäre Dyskinesie e. V.

Diagnostics of primary ciliary dyskinesia

Recommendations in cooperation with the Kartagener’s Syndrome and Primary Ciliary Dyskinesia Association

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Zusammenfassung

Charakteristika

Die primäre ziliäre Dyskinesie (PCD) ist eine seltene angeborene Erkrankung der Zilien, die sich zumeist im respiratorischen System manifestiert.

Diagnostik

Bei klinischem Verdacht auf das Vorliegen einer PCD und/oder bei positivem Screening (erniedrigte nasale NO-Werte) sollten Patienten zeitnah weitere diagnostische Maßnahmen durchlaufen. In Zentren, in denen eine Hochfrequenzvideomikroskopieanalyse (HVMA) des Zilienschlags zur Verfügung steht, ist eine initiale nasale NO-Messung zum Screening nicht zwingend erforderlich. Als erste diagnostische Maßnahme zur Sicherung oder zum Ausschluss einer PCD sollte eine HVMA erfolgen. Bei auffälligem Befund sind eine transmissionselektronenmikroskopische Analyse (TEM) der Ultrastruktur und eine hochauflösende immunfluoreszenzmikroskopische Analyse (IF) der Zilien anzuschließen. Obligat für die Diagnosestellung sind mindestens 2 kongruente pathologische Befunde aus HVMA, TEM oder IF. Wenn eine PCD-Variante ohne Hinweis auf einen ultrastrukturellen Defekt vorliegt, muss ein identischer pathologischer Zilienschlag mittels HVMA an insgesamt 3 unabhängigen Terminen belegt werden. Danach sollte auf Basis der erhobenen Befunde für HVMA, TEM und IF eine gerichtete genetische Abklärung angestrebt werden. Ein eindeutiger genetischer Befund kann die Diagnose ebenfalls sichern.

Vorgehen

Bei Verdacht auf eine PCD soll Kontakt mit einem Diagnosezentrum aufgenommen werden. Ein Referenzzentrum für PCD-Diagnostik evaluiert unklare Befunde.

Abstract

Characteristics

Primary ciliary dyskinesia (PCD) is a rare congenital disease of the cilia which is mostly manifested in the respiratory system.

Diagnostics

When there is a clinical suspicion of the presence of PCD and/or a positive screening result with reduced nasal nitrogen oxide (NO) values, further diagnostic measures should be initiated as soon as possible. In centers where high-frequency video microscopy analyses (HVMA) of beating of cilia are available, an initial nasal NO measurement for screening must not necessarily be carried out. As the first diagnostic measure for confirmation or exclusion of PCD, HVMA should be carried out. If the findings are conspicuous transmission electron microscopic analysis (TEM) of the ciliary structure and high-resolution immunofluorescence (IF) microscopic analysis of the cilia should follow. Mandatory for diagnosis are at least two congruent pathological findings from HVMA, TEM or IF. When a PCD variant with no evidence of ultrastructural defects is present, an identical pathological beating of cilia must be demonstrated with HVMA on three independent occasions. Following that a targeted genetic clarification should be attempted based on the findings for HVMA, TEM and IF. A clear genetic result can also confirm the diagnosis.

Approach

When PCD is suspected contact with a diagnostic center should be made. A reference center for PCD diagnostics will evaluate uncertain findings.

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Abb. 1

Abbreviations

ATS:

American Thoracic Society

DNA:

Desoxyribonukleinsäure

DRC:

Dyneinarmregulatorkomplex

EDTA :

Ethylendiamintetraessigsäure

ERS:

European Respiratory Society

HVMA :

Hochfrequenzvideomikroskopieanalyse

IDA:

„Inner dynein arm“

IF :

Immunfluoreszenz

KS:

Kartagener-Syndrom

NO:

Stickstoffmonoxid

ODA:

„Outer dynein arm“

PCD:

„Primary ciliary dyskinesia“

ppb:

„Parts per billion“

RDS:

„Respiratory distress syndrome“

RPMI:

„Roswell Park Memorial Institute medium“

TEM:

Transmissionselektronenmikroskopie

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Authors and Affiliations

  1. Klinik für Kinder- und Jugendmedizin Koblenz und Mayen, Koblenzer Straße 115–155, 56073, Koblenz, Deutschland

    T. Nüßlein

  2. Klinik für pädiatrische Pneumologie, Allergologie und Neonatologie, Zentrum für Kinder- und Jugendmedizin, Medizinischen Hochschule Hannover, Carl- Neuberg Straße 1, 30625, Hannover, Deutschland

    F. Brinkmann

  3. Darmstädter Kinderklinik Prinzessin Margaret, Dieburgerstraße 31, 64287, Darmstadt, Deutschland

    P. Ahrens

  4. Institut für Pathologie, Städtisches MVZ (Medizinisches Versorgungszentrum) Kiel, Chemnitzstraße 33, 24116, Kiel, Deutschland

    M. Ebsen

  5. Kinderspital Zürich, Universitäts-Kinderkliniken, Steinwiesstraße 75, 8032, Zürich, Schweiz

    A. Jung

  6. Selbsthilfeverein Kartagener Syndrom und Primäre Ciliäre Dyskinesie e. V., Traubenweg 67, 3612, Steffisburg, Schweiz

    W. Kirchberger, A. Kneißl & J. Sendler

  7. Klinik für Kinder- und Jugendmedizin, St. Josef-Hospital, Ruhr-Universität Bochum, Alexandrinenstraße 5, 44791, Bochum, Deutschland

    C. Koerner-Rettberg

  8. Praxis für Physiotherapie, von-der Tann-Straße 16, 97688, Bad Kissingen, Deutschland

    H. Linz-Keul

  9. Allgemeine Pädiatrie, Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Deutschland

    N.T. Loges, C. Werner &  H. Omran

  10. Institut für Pathologie und Neuropathologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45122, Essen, Deutschland

    D. Theegarten

  11. Klinik für Neugeborene, Kinder und Jugendliche, Klinikum Süd, Breslauerstraße 201, 90471, Nürnberg, Deutschland

    H. Seithe

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  1. T. Nüßlein
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  2. F. Brinkmann
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  3. P. Ahrens
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  4. M. Ebsen
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  5. A. Jung
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  13. J. Sendler
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  14. C. Werner
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  15. H. Omran
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Correspondence to H. Omran.

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Nüßlein, T., Brinkmann, F., Ahrens, P. et al. Diagnostik der primären ziliären Dyskinesie. Monatsschr Kinderheilkd 161, 406–416 (2013). https://doi.org/10.1007/s00112-012-2798-y

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