Knowledge

There are many manifestations of CF that can suggest the diagnosis.

Presentations

Prenatal Diagnosis

Pregnant women may have a simple blood test to look for common mutations (abnormalities) in the CFTR gene that cause cystic fibrosis (CF). If she carries one CFTR gene mutation. There is a 50 percent chance that this CFTR gene mutation will be passed on to the baby. If the father is also a carrier of a CFTR gene mutation there is a 25 percent (1 in 4) chance that the baby will have CF. Amniocentesis or chorionic villus sampling (CVS) sampling can be used for prenatal diagnosis of the baby. Prenatal screening does not test for all the known CFTR gene mutations, therefore, children can still be diagnosed with CF even if prenatal testing was normal or negative.

Inheritance pattern of normal or mutated CFTR genes from parents.

Inheritance pattern of normal (N) or mutated (M) CFTR genes from parents who carry an abnormal copy of the CFTR gene.

Newborn Screening

Newborn screening

All 50 states perform newborn screening of infants to test for hypothyroidism, phenylketonuria, and several other diseases, including CF. The newborn screen tests a small amount of blood, usually obtained from the baby’s heel. The goal of newborn screening is to diagnose CF before any symptoms develop. Newborn screening tests vary from state to state. Maryland added a test for CF to its newborn screening program in 2006. Not all infants with a “positive” newborn screen have CF. Therefore, infants with a “positive” newborn screening test for CF should be referred for a sweat test to confirm the diagnosis.

Additionally, newborn screening does not detect all children with CF. Therefore, children with symptoms that could be caused by CF should be evaluated with a sweat test even if the newborn screening was “normal” or “negative.”

Meconium Illeus

Approximately 18 percent of infants with CF present with meconium ileus (MI), which is an obstruction of the bowel caused by thick, abnormal meconium. Meconium ileus is suspected if a baby fails to pass meconium shortly after birth and develops symptoms of a bowel obstruction, such as abdominal distention or vomiting. Meconium ileus can lead to bowel perforation, a twisting of the bowel, or inflammation and infection in the abdomen.

Meconium ileus must be treated immediately to prevent complications. In some cases, enemas can be used to flush out the meconium. However, in severe cases, surgery is required to remove the obstruction. All babies with meconium ileus should be tested for CF because 98 percent of full-term babies with meconium ileus have CF.

A hyperechoic or echogenic bowel pattern is a prenatal ultrasound finding that suggests an intestinal obstruction caused by abnormal meconium. Among fetuses who have a prenatal ultrasound with hyperechoic bowel, about 1 in 10 will have CF and meconium ileus. In pregnancies where there is evidence of fetal bowel obstruction on prenatal ultrasound, both parents can be tested to find out if they carry CFTR gene mutations. Sometimes an echogenic bowel is a transient finding that resolves by the third trimester.

meconium ileus

A. Illustration of intestine blocked by meconium. B. Abdominal x-ray of a newborn infant with meconium ileus showing dilated loops of bowel.

Respiratory Problems

Normal lung airway compared with lung airway with CF

Compare the normal lung airway to the lung airway with CF and bacterial infection or with CF and inflammation.

The respiratory problems associated with CF can present at any age, and can affect both the upper and lower respiratory tracts. Recurrent or chronic sinus infections are common in people with CF. The possibility of CF should be considered in individuals with severe sinus disease or nasal polyps. Sinus CT scans of people with CF almost always show abnormal sinus cavities full of mucus.

Recurrent respiratory symptoms or infections may suggest the diagnosis of CF. The most prominent feature of lower respiratory tract disease in CF is a chronic cough. Sputum production is present in more severe lung disease.

Chest x-rays often show hyperinflation, small collapsed portions of the lung, mucus pugging or infection. People with CF may be affected by recurrent pneumonia, bronchitis and/or wheezing. Bronchiectasis can be observed in CT scans of the chest. Airways infection with certain bacteria such as Pseudomonas aeruginosa also suggest the diagnosis of CF.

Gastrointestinal Problems

Pancreatic Insufficiency

The gastrointestinal tract is frequently affected in CF. Approximately 80 percent of individuals with CF have pancreatic insufficiency. In these people, abnormal secretions block the passages within the pancreas leading to scarring and inadequate enzyme excretion into the intestine. Pancreatic insufficiency leads to malabsorption, (improper digestion of food) especially fats and difficulty gaining weight. In children, poor weight gain often results in growth below the standard growth curves and is called failure to thrive. Children with failure to thrive should be tested for CF, especially if they have abnormal stools or respiratory problems.

Signs and Symptoms of Malabsorption
Abdominal Bloating
Abdominal Pain
Cramping
Fat soluble vitamin (A, E, D, and K) deficiency
Flatulence (excess gas)
Frequent bulky, greasy or oily, or foul-smelling stools (Steatorrhea)
Malnutrition or poor weight gain

Unusual Presentations

CFTR-Related Disorder

Most individuals with CF have respiratory and gastrointestinal problems. However, some people without the usual features of CF may have a “positive” (abnormal) or intermediate sweat test. They may have only one or no known CFTR gene mutations, instead of the two mutations seen in most people with CF. The diagnosis of CFTR-related disorder is applied to these people with these atypical presentations. Symptoms of CFTR-related disorder may include chronic sinus disease, nasal polyps, pancreatitis, or males infertility. Individuals with atypical CF presentations usually do not have pancreatic insufficiency and they are often diagnosed at an older age.

Chronic Sinus Disease

The sinuses are affected in almost all individuals with CF. CT scans of the sinuses  almost always show abnormalities including sinuses filled with mucus or pus rather than air. Recurrent sinus infections can be a sign of CF, especially if caused by certain bacteria such as Pseudomonas aeruginosa.

The mucosa, or lining, of the nasal passages in people with CF is often red and swollen. Nasal polyps may develop in this inflamed nasal mucosa. Symptoms of nasal polyps include stuffy nose, mouth breathing, snoring, nasal pain, change in voice, distortion or widening of the nasal bridge, or nose bleeds. Because nasal polyps are uncommon in the general population, individuals with nasal polyps should be tested for CF.

Pancreatitis

Acute pancreatitis has been reported in about 15 percent of individuals with CF.  Symptoms include severe abdominal pain and vomiting. People with pancreatitis may or may not have chronic pulmonary symptoms. Individuals with pancreatitis typically produce adequate pancreatic enzymes and are not affected by malabsorption or failure to thrive.

Congenital Bilateral Absence of the Vas Deferens (CBAVD)

Congenital bilateral absence of the vas deferens (CBAVD) leads to the absence of sperm (azoospermia) in men with CF. Almost all post-pubertal males with CF have azoospermia, leading to infertility. Some men with CBAVD due to CFTR gene mutations have no other features of CF. These individuals may have normal, intermediate, or elevated sweat chloride concentrations. People with CBAVD should be monitored for the development of other CF-related complications.