Fibrosi cistica
Definizione
La fibrosi cistica è una malattia autosomica recessiva in cui è alterato il gene CFTR, cioè il regolatore della conduttanza transmembrana della fibrosi cistica. Il gene è stato scoperto nel 1989. Coloro che sono affetti da fibrosi cistica hanno ereditato un gene difettoso sia dal padre sia dalla madre che sono, senza saperlo, portatori sani del gene CFTR mutato. Si stima che ogni 2.500-3.000 dei bambini nati in Italia,1 è affetto da fibrosi cistica (200 nuovi casi all’anno).
Manifestazioni cliniche
La fibrosi cistica colpisce soprattutto l’apparato respiratorio e quello digerente.
Apparato respiratorio
Accumulo di muco denso e appiccicoso, infezioni polmonari frequenti e tosse o mancanza di respiro. Inizialmente la malattia polmonare si limita a un’ infiammazione delle vie aeree, compresi i bronchi e bronchioli, durante la fase acuta fa seguito una progressiva cronicizzazione delle lesioni che porta alla stasi delle secrezioni nelle vie più fini. L’interessamento del parenchima può andare da:
- atelettasia
- fibrosi
- iperdistensione
- bolle enfisematose
- pneumomediastino
- emotorace
In qualche caso si fa evidente il quadro dell’asma, specialmente quando nelle vie aeree si trova l’ aspergillus. La malattia cronica polmonare può portare all’instaurarsi di un cuore polmonare cronico.
Apparato gastrointestinale
Circa l’ 85% dei pazienti ha mal digestione, come conseguenza dell’ insufficienza del pancreas esocrino, che comprenderà anche l’emissione di feci abbondanti, lucide, maleodoranti.
Apparato genito-urinario
I soggetti affetti da fibrosi cistica sono poco fertili e generalmente hanno una predisposizione alla litiasi renale. La calcolosi renale ha nella fibrosi cistica una prevalenza quasi doppia (6,3% contro il 3%), rispetto alla popolazione generale. Vi sono nella fibrosi cistica alcuni fattori predisponenti tra cui:
- l’eccesso di eliminazione di acido urico (iperuricosuria)
- l’eccesso di eliminazione di ossalato (iperossaluria, per difetto di colonizzazione intestinale da parte di un batterio che degrada nell’intestino gli ossalati) .
Diagnosi
Nei tempi antichi nell’Europa del Nord, durante la cerimonia di purificazione, si era soliti leccare la fronte dei neonati e bambini. Se veniva percepito un sapore salato, il bambino veniva detto stregato o destinato a morte precoce. Un antico proverbio tedesco recitava “morirà presto il bambino, la cui fronte di sale si è baciata“. In tal modo, la saggezza popolare aveva già anticipato quanto l’osservazione medica avrebbe poi scoperto negli anni 50 e la ricerca scientifica non ancora completamente chiarito. Infatti il testo di questo antico proverbio tedesco ci indica che è nella concentrazione di sali nel sudore la diagnosi per la fibrosi cistica. E’ proprio questa caratteristica del sudore particolarmente salato, avvertito dalle madri quando baciavano i bambini affetti,che farà chiamare la fibrosi cistica “la malattia del bacio salato”.
La diagnosi oggi si basa sulla presenza di manifestazioni cliniche o biochimiche compatibili con la malattia, in associazione alla positività che almeno uno tra i testi diagnostici validati che comprendono:
- il test del sudore (con cloro e sodio in concentrazione superiore alla norma)
- lo studio della differenza di potenziale elettrico transepiteliale nelle mucose respiratorie o intestinali
- l’analisi genetica che si considera positiva quando identifico prenotazioni che causano la fibrosi cistica.
Screening neonatale
Lo screening neonatale per fibrosi cistica si compone di un sistema di analisi a più livelli (step). Il primo step consiste nel dosaggio del tripsinogeno immunoreattivo (IRT) in tutti i neonati. Nei neonati con valore di IRT superiore al 98° centile viene eseguita l’analisi molecolare delle mutazioni più rappresentate localmente (secondo step). La presenza di due mutazioni consente di porre diagnosi di fibrosi cistica, qualora se ne individui una sola il neonato viene richiamato e sottoposto al test del sudore (terzo step) per una conferma o smentita diagnostica definitiva. Il problema si pone quando ci si trova di fronte un IRT positivo, una mutazione e il test del sudore negativo. Alcuni di questi neonati sono eterozigoti composti, in cui la seconda mutazione è una mutazione rara e, pur essendo negativi al test del sudore, possono essere affetti da forme atipiche di fibrosi cistica o da altre patologie correlate ad anomalie del gene CFTR.
Fibrosi cistica- Trattamento-Wikipedia
Dita ippocratiche nelle dita di una persona con fibrosi cistica
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