Cystic Fibrosis (CF)
Cystic Fibrosis is an autosomal recessive genetic disorder characterized by severe lung damage and nutritional deficiencies. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes the body to produce thick, sticky secretions that obstruct passageways in the lungs and pancreas leading to:
- Lung infections and respiratory failure
- Blockage of pancreatic enzymes that lead to malnutrition
- Infertility in affected males
The most common mutation causing CF is a three-base pair deletion in the position of delta F508 (dF508), but there are now over 1800 mutations identified in the CFTR gene.
The identification of increased immunoreactive trypsinogen (IRT) levels in the blood of infants with CF has made neonatal screening for CF possible. Trypsinogen is one of the secretory products of the pancreas making its level in the blood a specific marker of pancreatic function. Detection of high levels of IRT in the newborn period place the infant at risk for CF. Although there is no cure, newborns screened for cystic fibrosis can benefit from early diagnosis and treatment, which can:
- Improve growth
- Improve lung function
- Reduce hospital stays
- Add years to life
While newborn screening is not a definitive diagnostic test for cystic fibrosis, it can lead to confirmatory sweat testing that can rule out or confirm a CF diagnosis. The Cystic Fibrosis Foundation and the Centers for Disease Control and Prevention recommend cystic fibrosis screening for all newborns.
Primary test - Analyte measured: Immunoreactive Trypsinogen (IRT). Immunofluoresence Assay.
Secondary test - CFTR mutation testing for the 39 most common CF mutations, including the 23 mutations recommended by the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG).
NBS (Newborn Screening) for cystic fibrosis is done in a two-step process. First, the newborn will have an IRT assay performed. If the IRT level is elevated, then the newborn will have a second assay performed on the same dried blood spot sample to detect if any CF mutations are present. This two step screen provides earlier detection of newborns with cystic fibrosis, therefore allowing for quicker diagnosis.
Missouri newborn screening samples must only be collected on the Food and Drug Administration (FDA) approved blood collection forms that must be pre-purchased from the MSPHL. The optimum collection time is between 24 and 48 hours-of-age. The instructions for collecting the samples are listed on the back of the collection form. All 5 circles on the filter paper need to be filled with blood from one side and then air dried for at least 3 hours in a horizontal position without allowing the blood to touch any surface during drying, including other parts of the card (see image).
See "Rules for Collection".
Store the dried blood samples at room temperature in the envelopes provided by the MSPHL and transport within 24 hours of collection.
Acceptable Specimen Type(s)
Initial Screen (the red form) or Repeat Screen (the green form)
Test Request Form(s)
Included in kit
Normal - No action required.
Borderline IRT - These results are in the borderline risk range. A prompt repeat newborn screen is necessary after 7 days of age, but no later than 90 days of age. The Immunorective Trypsinogen (IRT) result is slightly elevated. The final report will be mailed to the physician of record.
Abnormal, No CF mutations were detected - No mutations were detected using the current screening panel. Cystic Fibrosis is not likely. No further evaluation necessary unless clinically indicated. The final report will be mailed to the physician of record.
Abnormal, One CF mutation was detected - Referral to an accredited CF Center for consultation and sweat testing is necessary. One mutation in the screening panel was identified. The Immunoreactive Trypsinogen (IRT) is elevated. Cystic Fibrosis cannot be ruled out due to the possibility of a second mutation which is not included in the screening panel. The final newborn screening report will be phoned and faxed to the physician/health care provider and appropriate CF center.
Abnormal, Two CF mutations were detected - Immediate referral to an accredited CF Center for consultation and sweat testing is necessary. Two mutations in the screening panel were identified. The Immunoreactive Trypsinogen (IRT) is elevated. The final newborn screening report will be phoned and faxed to the physician/health care provider and appropriate follow up center.
No Result - All specimens collected before 24 hours of age are invalid and are given a "No Result". A repeat newborn screen is requested.
All final newborn screening reports are mailed to the physician of record.
IRT concentration is frequently high immediately after birth, therefore specificity is improved if the test is performed after the first day of age. A specimen collected between 24 and 48 hours of age is optimal. There is also an age-related decline in IRT levels in children with CF. IRT levels within the normal range will be considered non-interpretable after 3 months of age and will not be reported on the newborn screen. IRT concentration is high in the blood of infants with CF, presumably from leakage of the protein into the circulation after exocrine pancreatic injury. Some infants that do not have CF may also have elevated levels of IRT in the newborn period, but these levels decrease to normal in the first weeks of life.
- Premature or sick infants may have a false-positive screen due to increased stress on the body.
- Blood collection with EDTA can result in inaccurate screening results.
- Babies with meconium ileus have an increased likelihood of having CF, but may not have elevated IRT levels in the newborn period.
- Specimens collected prior to 24 hours of age may exhibit a false positive or false negative result. It is extremely important to perform a second screening on these infants as soon as possible to ensure that the infant whose IRT level has not stabilized, and is continuing to rise, is not missed. A small percent of infants will be detected only on a second screen.
- Mild or atypical forms of CF may not demonstrate elevated IRT levels in the newborn period
1 to 5 working days.
$95 charge - for full panel of screening disorders
Prevalence of Disorder: 1:3,200 in Missouri
The newborn screening test for CF is meant to identify infants at risk for CF and in need of diagnostic sweat testing. A “normal” screen does not rule out the possibility of the disease. The health care provider should remain vigilant to detect CF among children with clinical symptoms.
Follow Up Testing and Treatment: If 1 or 2 CFTR mutations are detected, the baby's primary care physician will be contacted immediately with recommendations for immediate referral to an accredited CF Center for diagnostic sweat testing (pilocarpine iontophoresis). The Missouri Department of Health and Senior Services have contracted four accredited CF Centers for follow-up sweat testing, counseling and consultation (see below, "Missouri Certified CF Centers"). The final newborn screening report will be phoned and faxed to the physician/health care provider and appropriate CF center.
To receive optimal treatment, children with CF should be examined by Cystic Fibrosis Foundation certified CF centers that offer a comprehensive approach to CF care and that can closely monitor the development of respiratory infections and provide nutritional and psychosocial support. CF patients follow a strict regimen to treat the disease as well as care to reduce contracting outside infections. CF is inherited as an autosomal recessive disease, which means both parents are carriers of a mutation for the gene. Carrier testing for at-risk family members is available.
The treatment regimen can include:
- Oral and or IV Antibiotics to fight infections
- Vitamins to improve general health
- Respiratory therapy such as bronchodilators and other treatments to clean airways and dislodge mucus from the lungs
- Steroids to reduce inflammation
- Supplemental oxygen therapy
- Enzymes to aid in digestion
- Liquid nutrition or healthy high calorie diets for weight gain
- Counseling and support
Missouri Certified CF Centers:
Cardinal Glennon Children's Medical Center (St. Louis, MO) 314-268-4107
Children's Mercy Hospital (Kansas City, MO) 816-983-6490
St. Louis Children's Hospital (St. Louis, MO) 314-454-2353
University Hospitals and Clinice (Columbia, MO) 573-884-8579
CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). This gene helps create sweat, digestive juices, and mucus. Since the identification of the gene and the major mutation responsible for CF, more than 1800 mutations and DNA sequence variations have been identified in the CFTR gene. The Delta F508 mutation is represented in almost all populations, although its relative frequency varies among different geographic locations. The highest frequency is observed in Caucasian populations, where it accounts for approximately 70 percent of the CF alleles.
Because CF is an autosomal recessive genetic disorder, an individual must have two mutated CFTR genes to express the disease phenotype (one abnormal gene inherited from each parent). An individual with one normal gene and one abnormal gene is a CF carrier. Carriers do not have symptoms and are not ill. Different CFTR mutations result in different disease phenotypes. Some may have little or no effect on CFTR function, and some may result in milder forms of disease. Even siblings with identical CF mutations may have dramatically different clinical courses. CF may affect the lung and upper respiratory tract, GI tract, pancreas, liver, sweat glands, and genitourinary tract. Nutritional abnormalities secondary to pancreatic insufficiency also have predictable consequence for growth and development.
Signs and Symptoms Associated with CF Include:
Because there are more than 1800 mutations of the CF gene, symptoms differ from person to person.
Symptoms in newborns may include:
Failure to thrive - large appetite but failure to gain weight or grow at a normal rate
No bowel movements in first 24 to 48 hours of life
Symptoms related to bowel function may include:
Belly pain from severe constipation
Increased gas, bloating, or a belly that appears swollen (distended)
Nausea and loss of appetite
Stools that are pale or clay colored, foul smelling, have mucus, or that float
Weight loss or malnutrition
Symptoms related to the lungs and sinuses may include:
Increased coughing or increased mucus in the sinuses or lungs
Nasal congestion caused by nasal polyps or infection
Recurrent episodes of pneumonia
Increased shortness of breath