Atypical cystic fibrosis: from the genetic causes to current and future treatments
Quinn, Ryan Kelley
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Cystic Fibrosis (CF) is a life threatening autosomal recessive disorder caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to irregular secretions and inflammation in tubular organs. Disease manifestations of CF are heterogeneous in severity and can be present in the sinopulmonary, hepatic, gastrointestinal, and genitourinary tract. Since the 1960’s, physicians and scientists have described a less severe form of CF known as atypical CF, usually seen in adults. Patients with atypical CF tend to have one severe CF mutation on one chromosome, and one less common, mild CF mutation on their other chromosome; or have one severe mutation on one chromosome and an abnormal number of trinucleotide repeats in the CFTR gene on their other chromosome. Today, of the approximately 1000 patients diagnosed with CF per year in the United States, roughly 10% are diagnosed with the atypical presentation of the disease as adults. Patients suffering from atypical CF typically have only one organ system that is dysfunctional, and their clinical symptoms may be less severe than those of a classical case where there are two severe CF mutations. Common symptoms include idiopathic bronchiectasis, chronic sinusitis, congenital bilateral absence of the vas deferens (CBAVD), and idiopathic pancreatitis. Unlike patients suffering from the classical presentation of the disease, most are pancreatic sufficient – however the possibility of pancreatic insufficiency still exists. Patients with atypical CF represent a diagnostic challenge for physicians due to the mild, slowly progressing array of clinical symptoms, the general lack of knowledge about atypical CF, and the general association of CF as a childhood disease. Increasing physician awareness of the adult population with CF is a paramount in improving the diagnosis, care and treatment of patients with atypical CF. Missed diagnoses can result in hospital admissions and morbidity that may have been avoidable. The goal of this thesis is to describe the causes of CF, the common symptoms seen in both CF and atypical CF, the proper diagnosis of atypical CF, and to identify the therapies, both current and in development, used to treat atypical CF.