Review Question - QID 217663

This patient with a history of meconium ileus, persistent cough, recurrent sinusitis, steatorrhea, nasal polyposis, failure to thrive, and crackles on lung examination most likely has cystic fibrosis (CF). Infertility is an extremely common complication of CF, present in over 95% of men with CF.

Cystic fibrosis is an autosomal recessive disorder caused by a mutation in the gene that encodes the cystic fibrosis conductance regulator (CFTR) protein. This leads to defective chloride channels, which in turn can manifest with pulmonary symptoms (frequent respiratory infections, thickened alveolar secretions, chronic sinusitis, nasal polyposis), gastrointestinal symptoms (pancreatic insufficiency, steatorrhea, meconium ileus), failure to thrive, excessively salty skin, and decreased fertility. CFTR plays a critical role in the development of structures derived from the mesonephric (Wolffian) duct, most commonly the vas deferens. Clinically, this leads to infertility in over 95% of men with CF. Importantly, spermatogenesis is unaffected in men with CF; therefore, microsurgical epididymal sperm aspiration can allow affected men to be biological fathers. Women with CF are often sub-fertile, largely due to thickened cervical mucus and malnutrition.

Shteinberg et al. review the pathophysiology, epidemiology, clinical presentation, diagnosis, management, and complications of cystic fibrosis. They discuss how the disease may present in only one organ if there is residual gene function. They recommend continuing research on small molecule modulators that aim to restore gene function may transform the treatment of this disease.

Incorrect Answers:
Answer 1: Cholelithiasis has been reported in 10-15% of CF patients due to excessive loss of bile acids in the stool. This leads to the production of lithogenic bile and cholelithiasis. A minority of patients with CF may also have biliary cirrhosis, which can lead to progressive liver disease with periportal fibrosis, cirrhosis, portal hypertension, and variceal bleeding. This is less prevalent than infertility in men with CF.

Answer 3: Left heart failure has not been definitively associated with CF. However, severe lung disease in patients with CF can lead to right-sided heart failure (cor pulmonale). This would present with peripheral edema and jugular venous distention.

Answer 4: Nasopharyngeal carcinoma has not been associated with CF. Although CF can lead to chronic sinusitis and nasal polyposis as seen in this patient, this does not typically develop into cancer. CF has been associated with an increased incidence of gastrointestinal cancers.

Answer 5: Rectal prolapse occurs rarely in children with CF. In the past, rectal prolapse was present in 20% of patients with classic CF, most likely due to the underuse of pancreatic enzyme therapy. However, in this patient receiving pancreatic enzyme supplementation, rectal prolapse would be an uncommon complication.

Bullet Summary:
Infertility due to the congenital absence of the vas deferens is an extremely common complication in men with cystic fibrosis.