Fast Five Quiz: Inherited Conditions

Germaine L. Defendi, MD

Disclosures

October 29, 2018

Pancreatic insufficiency is the most common gastrointestinal complication of cystic fibrosis. Approximately 85%- 90% of patients with cystic fibrosis develop this complication at some point in their lives. Pancreatic insufficiency leads to fat malabsorption due to decreased pancreatic enzyme production. As a result, patients are at risk for steatorrhea, malnutrition, and fat-soluble vitamin deficiencies. However, patients diagnosed late in childhood or in adulthood are more likely to have pancreatic sufficiency and often present with a clinical history of chronic cough and sputum production instead. About 10% of patients with cystic fibrosis remain pancreatic sufficient; these patients tend to have a milder disease course.

Median age at diagnosis of cystic fibrosis is 6- 8 months; two thirds of patients are diagnosed by age 1 year. The age at diagnosis widely varies, as do clinical presentation, severity of symptoms, and rate of disease progression in the organs involved. Neonates may present with meconium ileus, prolonged neonatal jaundice, or, rarely, anasarca. Patients younger than 1 year may present with wheezing, coughing, and/or recurrent respiratory infections and pneumonia. Clinical findings associated with gastrointestinal involvement may present as steatorrhea, failure to thrive, or both.

Because cystic fibrosis is inherited in an autosomal recessive fashion, two copies of the abnormal gene, CFTR (cystic fibrosis transmembrane conductance regulator), must be present in an individual for clinical disease to occur. The CFTR gene is cytogenetically located on the long arm of chromosome 7q, band 31.2. The six types of defects that can result from CFTR mutations are:

  • Complete absence of CFTR protein synthesis

  • Defective protein maturation and early degradation

  • Disordered regulation (diminished ATP binding and hydrolysis)

  • Defective chloride conductance or channel gating

  • Diminished transcription due to promoter or splicing abnormality

  • Accelerated channel turnover from the cell surface

Because of the poor penetrance of CFTR mutations, genotypes associated with cystic fibrosis do not help predict disease pattern or severity.

Chronic sinopulmonary disease is a hallmark of cystic fibrosis. After age 5 years, panopacification of the sinuses viewed on plain radiography is present in most patients. Specifically, more than 75% opacification of the maxillary and ethmoid sinuses is considered a hallmark of cystic fibrosis. Abnormal paranasal sinuses, defined as lateral nasal wall bulging near the middle meatus and resorption of nasal bone structures, is considered a distinctive feature of cystic fibrosis sinusitis. Conversely, absence of pansinusitis on imaging studies strongly suggests that cystic fibrosis is not present.

The Pulmonary Therapies Committee of Cystic Fibrosis Foundation recommends long-term use of hypertonic saline for patients aged 6 years or older with cystic fibrosis   to improve lung function and reduce frequency of pulmonary exacerbations. A controlled trial of long-term use of inhaled 7% hypertonic saline in patients with cystic fibrosis found no association between its use and worsening pulmonary bacterial infections or inflammation. This study concluded that inhaled hypertonic saline preceded by a bronchodilator is an inexpensive, safe, and effective additional therapy for patients with cystic fibrosis.

For more information on cystic fibrosis, read here.

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