20.7
Mukoviszidose: Pathogenese
Mukoviszidose (CF), eine autosomal-rezessive Erkrankung, beeinträchtigt die Funktion der exokrinen Drüsen erheblich. Diese genetisch bedingte Krankhei…
Mukoviszidose (Mukoviszidose) ist eine autosomal-rezessive Erkrankung, die auf Mutationen im Mukoviszidose-Transmembran-Leitfähigkeitsregulator (CFTR-Gen) auf Chromosom 7 zurückzuführen ist.
Mukoviszidose stammt von über 2000 Mutationen innerhalb des CFTR-Gens.
Das CFTR-Protein fungiert als Ionenkanal und reguliert den Chlorid- und Natriumionentransport in schleimproduzierenden Zellen.
Die Mutationen können zu einer verminderten Chloridsekretion und einer erhöhten Natriumabsorption führen, wodurch dickerer Schleim entsteht und die Atemwege beeinträchtigt werden.
Anfangs erscheint die Lunge eines CF-Patienten normal, aber ein Kaskadeneffekt, gefolgt von einer Infektion und Entzündung, führt dazu, dass sich der Schleim in den Bronchiolen verstopft und eine obstruktive Lungenerkrankung verursacht.
Mukoviszidose kann klinisch chronischer Bronchitis, Bronchiektasen, atypischem Asthma, allergischer bronchopulmonaler Aspergillose und Infektionen wie Pseudomonas aeruginosa ähneln.
Das diagnostische Screening umfasst Schweißchlorid-, DNA- und Nasenpotentialdifferenztests mit Bestätigung durch CF-bezogene Mutationstests.
Lungenfunktionstests sind entscheidend für die Überwachung des Krankheitsverlaufs.
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Q1: What genetic mutation causes cystic fibrosis?
Cystic fibrosis results from mutations in the CFTR gene on chromosome 7, with over 2,000 known mutations identified. The most common mutation is ΔF508. These mutations disrupt the CFTR protein, which normally functions as an ion channel regulating chloride and sodium transport in mucous-producing cells, leading to thick, sticky mucus production.
Q2: How do CFTR mutations affect ion transport and mucus production?
CFTR mutations cause decreased chloride secretion and increased sodium absorption in mucous-producing cells. This ion imbalance reduces water secretion into mucus, resulting in thicker, more viscous secretions. The abnormal mucus accumulates in airways and ducts, obstructing normal function across multiple organ systems.
Q3: What happens to the lungs in cystic fibrosis patients?
Initially, CF lungs appear normal, but mutations trigger a cascade of infection and inflammation. Thick mucus plugs the bronchioles, causing obstructive lung disease. CF lung disease clinically resembles chronic bronchitis, bronchiectasis, and can involve colonization with Pseudomonas aeruginosa, leading to progressive airway damage.
Q4: Which organs are most commonly affected by cystic fibrosis?
CF primarily affects exocrine glands and multiple organ systems. The most commonly affected organs include sinuses, lungs, pancreas, liver and biliary systems, intestines, and sweat glands. Pancreatic involvement causes insufficiency and early-onset diabetes, while hepatobiliary manifestations include cirrhosis and portal hypertension.
Q5: How is cystic fibrosis diagnosed?
CF diagnosis requires clinical symptoms, positive family history, and confirmatory tests. The sweat chloride test measures elevated chloride levels in sweat. DNA testing identifies two disease-causing CFTR mutations, and nasal potential difference testing measures abnormal ion transport. Pulmonary function tests monitor disease progression and lung involvement.
Q6: What respiratory complications can develop from cystic fibrosis?
CF can clinically resemble chronic bronchitis, bronchiectasis, atypical asthma, and allergic bronchopulmonary aspergillosis. Mucus plugging in bronchioles causes obstructive airway disease and chronic infections. Abnormal pulmonary function tests reflect progressive lung damage, and bacterial colonization, particularly Pseudomonas aeruginosa, accelerates respiratory decline.
Q7: Why is cystic fibrosis classified as an autosomal recessive disorder?
CF is autosomal recessive because the CFTR gene mutation on chromosome 7 requires two mutated copies—one from each parent—for disease expression. Individuals with one mutated copy are carriers but typically asymptomatic. This inheritance pattern means affected individuals have carrier parents, and siblings have a 25% chance of inheriting the disease.