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10.1016/BN02-9783437223853.10001-8
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Abb. N2-1

Algorithmus bei klinischem Verdacht auf Mukoviszidose
Mutationen mit einer Häufigkeit von ≥ 1% nach dem WHO-Report von 2004 (1)
Deutschland | Österreich | Schweiz |
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Diagnose der Mukoviszidose (S2k)
2.1
Einführung und Definitionen
2.1.1
Definitionen
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ein positives Neugeborenenscreening oder
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Geschwister mit Diagnose einer Mukoviszidose oder
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mindestens ein klinischer Hinweis auf eine Mukoviszidose.
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erhöhte Schweißchloridwerte (≥ 60 mmol/l) bei mindestens zwei unabhängigen Messungen oder
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Nachweis zweier Mukoviszidose verursachenden CFTR-Mutationen (in trans) oder
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Nachweis einer charakteristischen Abnormalität der CFTR-Funktion mittels nasaler Potenzialdifferenzmessung (NPD) oder intestinaler Kurzschlussstrommessung (ICM).
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obstruktive Azoospermie oder
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chronische Pankreatitis oder
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disseminierte Bronchiektasien.
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zwei CFTR-Mutationen unabhängig vom Schweißchlorid oder
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eine CFTR-Mutation und ein Schweißchlorid zwischen 30–59 mmol/l,
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davon maximal eine Mukoviszidose verursachende Mutation und
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mindestens eine für eine CFTR-assoziierte Erkrankung beschriebene Mutation.
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keine zwei Schweißchloridwerte ≥ 60 mmol/l vorliegen und
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kein Nachweis zweier Mukoviszidose verursachender Mutationen bei einer Komplettanalyse des CFTR-Gens und
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kein Nachweis einer charakteristischen Abnormalität der CFTR-Funktion mittels NPD und/oder ICM erfolgt.
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2.2
Klinische Hinweise auf eine Mukoviszidose
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Chronische sinopulmonale Erkrankungen
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Chronischer (> 3 Monate) Husten und/oder Sputumproduktion und/oder pfeifendes Atemgeräusch und/oder Trommelschlägelfinger
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Persistierende pathologische Bildgebungsbefunde (Bronchiektasien/Atelektasen/Infiltrate/Überblähung)
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Persistierenden Nachweis von Staphylococcus aureus/Haemophilus influenzae/Pseudomonas aeruginosa/Burkholderia-cepacia-Komplex in Atemwegssekreten
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Beidseitige, chronische Rhinosinusitis mit/ohne Nasenpolypen mit häufigen Exazerbationen im Kindes- und Jugendalter
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Gastrointestinale Erkrankungen
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Pankreas: exokrine Pankreasinsuffizienz bei Kindern, akut rezidivierende und/oder chronische Pankreatitis
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Intestinal: pränatal echogener Darm (Ultraschall), Mekoniumileus, Mekoniumpfropfsyndrom, Rektumprolaps, distal intestinales Obstruktionssyndrom
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Leber: Chronische Lebererkrankung, insbesondere bei klinischem oder histologischem Nachweis einer fokal biliären oder multilobulären Zirrhose und/oder portaler Hypertension, Cholelithiasis ohne hämatologische Erkrankung, verlängerter Neugeborenenikterus
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Ernährungsstatus: Dystrophie, Hypoproteinämie und Ödeme, Komplikationen aufgrund eines Mangels an fettlöslichen Vitaminen und/oder Zink
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Salzverlustsyndrom: Hypochlorämische Alkalose ohne Erbrechen bei Kindern
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Genitale Erkrankung: Obstruktive Azoospermie
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Obstruktive Azoospermie
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Chronische Pankreatitis
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Disseminierte Bronchiektasien
2.3
Diagnostik
2.3.1
Schweißtest
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Durchführung nach Gibson-Cook oder mittels Macroduct-System®
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Stimulation der Haut mit Pilokarpin (Dauer 5 Min.) mittels batteriebetriebener Spannungsquelle
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Schweißsammelzeit (30 Min.)
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Schweißmindestmenge (≥ 1 g/qm Sammelfläche/Min. Sammelzeit)
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Mindestmenge für Gibson-Cook-System: z.B. 71 µl bei Filterpapier mit einem Durchmesser von 5,5 cm
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Mindestmenge für Macroduct-System®: 15 µl
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Analyse auf Chlorid mittels manueller oder koulometrischer Titration
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Beurteilung des Chloridwerts
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≤ 29 mmol: unauffällig = Mukoviszidose unwahrscheinlich
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30–59 mmol/l: Kontrollbereich = Weitere Diagnostik auf Mukoviszidose erforderlich
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≥ 60 mmol/l: vereinbar mit der Diagnose Mukoviszidose
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Ausreichende Erfahrung des Personals (> 50 Untersuchungen pro Zentrum pro Jahr, > 10 Untersuchungen pro Untersucher pro Jahr)
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Mitführen von Kontrollproben bei der Chloridbestimmung
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Kontrolle der Anzahl unzureichender Schweißstimulationen (Ziel < 5% unzureichende Schweißsammlungen bei Patienten älter als 3 Monate)
2.3.2
Molekulargenetische Diagnostik
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die CFTR-Synthese und/oder -Funktion deutlich beeinträchtigt wird,
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ein vorzeitiges Stopp-Kodon eingefügt wird (Insertionen, Deletionen, Nonsense-Mutationen),
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eines der invarianten Nukleotide GT/AG intronischer Spleißstellen betroffen ist,
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ein oder mehrere Exons deletiert sind.
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2.3.3
Elektrophysiologie
2.4
Konsequenzen der Diagnose
2.5
Ausblicke und Implementierung
2.6
Danksagung
2.6.1
Verfahren der Konsensbildung
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Gesellschaft für Pädiatrische Pneumologie (GPP) = federführende Fachgesellschaft
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Deutsche Gesellschaft für Andrologie (DGA)
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Deutsche Gesellschaft für Kinderchirurgie (DGKCH)
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Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ) – Screeningkommission
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Deutsche Gesellschaft für Hals-Nasen-Ohrenheilkunde, Kopf- und Hals-Chirurgie (DGHNOKHC)
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Deutsche Gesellschaft für Humangenetik (GfH)
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Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG)
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Deutsche Gesellschaft für Neugeborenenscreening (DGNS)
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Deutsche Gesellschaft für Pneumologie (DGP)
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Deutsche Gesellschaft für Reproduktionsmedizin (DGRM)
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Deutsche Gesellschaft für Verdauungs- und Stoffwechselerkrankungen (DGVS)
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Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI)
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Gesellschaft für Pädiatrische Gastroenterologie und Ernährung (GPGE)
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Mukoviszidose e.V. (Patientenvertreter)
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Schweizerische Gesellschaft für Pädiatrische Pneumologie (SGPP)
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