1. Cystic Fibrosis: A Review for Healthcare Providers
Provided by the Indiana State Department of Health

2. Outline Fast facts about CF Diagnosis CFTR gene Newborn screening
Symptoms
Medical management / prognosis
Inheritance / recurrence risks

3. Fast facts about CF
Currently, there are approximately 30,000 people in the US with CF*
ISDH estimates that each year in Indiana, approximately 300 children with at least one CFTR mutation will be identified through newborn screening^
*Cystic Fibrosis Foundation Patient Registry Annual Data Report, 2005
^Based on annual live birth rate of 87,000 children

4. Frequency of CFTR mutations in ethnic groups*
Fast facts (cont.)
Frequency of CFTR mutations in ethnic groups*
Caucasians^
^CF is the most common autosomal recessive condition in Caucasians
1 in 25
carries at least one CFTR mutation
Hispanics
1 in 46
African-Americans
1 in 65
*Genzyme Genetics, 2006

5. Newborn screening for CF
All infants receive IRT screen as part of newborn screening (heelstick)
IRT = immunoreactive trypsin
Infants with IRT above cutoff identified by the IU Newborn Screening Laboratory will receive DNA testing
IU Newborn Screening Laboratory tests for a panel of 44 common CFTR mutations
Note: CF newborn screening does NOT test for all known CFTR mutations

6. Newborn screening (cont.)
If an infant is found to have an elevated IRT
and 1+ CFTR mutations:
IU Newborn Screening Laboratory will notify primary care physician
Phone call & letter
IU Newborn Screening Laboratory will notify ISDH
ISDH will contact PCPs to assist with:
Referring patients for sweat chloride testing
Referring patients to CF centers
Counseling / educating families

7. Timeline for referrals
Primary care physicians should refer infants with 2 identified mutations to a Cystic Fibrosis Center within 2 weeks for evaluation and treatment
Primary care physicians should refer infants with 1 identified mutation for sweat chloride testing within 2 weeks of receiving newborn screening result
ISDH recommends referring patients to Cystic Fibrosis Foundation (CFF) accredited laboratories for sweat chloride testing

8. Why refer to CFF-accredited labs?
Indiana has chosen to follow the national precedent by referring patients to CFF-accredited centers for sweat chloride testing and management
CFF-accredited laboratories meet nationally-accepted standards selected by the CFF in conjunction with the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS)

9. Why refer to CFF-accredited labs? (cont.)
National standards are imperative to ensure that sweat chloride test results are consistently accurate and reliable
Several different sweat chloride test procedures exist
Procedures not approved by CFF & CLSI have demonstrated high false-positive and false-negative rates
Collection procedure is highly sensitive
Other procedures are erroneous

10. What about children with one CFTR mutation?
All children with at least one identified CFTR mutation should be referred for sweat chloride testing

11. What about children with one CFTR mutation?
Children with one identified mutation are typically asymptomatic carriers...
...however, some children with a single mutation will have CF
Again, newborn screening does not test for all known CFTR mutations
Some children could have a common mutation (identified through newborn screening) and a rare mutation that is not included in newborn screening panel

12. CFTR gene Over 1,400 disease-causing mutations currently known
Most are rare
Found in a single family
Almost all are small deletions or “point mutations”
Note: CF newborn screening does NOT test for all known mutations
Most common mutation:  F508
Represents approximately 30 – 80% of all identified mutations in patients with CF
Results in “classic” features of CF if two copies are present

13. Features of CF Complex, multisystem disease Most commonly affects:
Respiratory system
Gastrointestinal system
Male reproductive system

14. Pulmonary system Chronic sinopulmonary disease
Chronic cough / sputum production
Wheezing
Persistent infections with:
P. aeruginosa
S. aureus
H. influenzae
B. cepacia complex
Abnormal chest X-rays
Digital clubbing

15. Gastrointestinal system
Pancreatic insufficiency (> 90% of patients)
Malabsorption
Especially of fats / fat-soluble vitamins
May lead to failure to thrive, skin rashes, anemia
Meconium ileus (15 – 20% of patients)
Pancreatitis
Hepatobiliary disease
Hypoproteinemia
Distal intestinal obstructions
CF-related diabetes (usually develops in teens)

16. Male reproductive system
> 95% males with CF are infertile
Abnormal development of Wolffian ducts leads to azoospermia
Testicular development / function and spermatogenesis are usually normal

17. Male reproductive system (cont.)
Congenital bilateral absence of vas deferens (CBAVD) can occur in males with specific CFTR mutations
Regardless of whether these males have other symptoms of CF
For more information, or with questions about specific gene changes, please contact ISDH
Contact information is provided at the end of this review

18. Medical management
Recommend referral to Cystic Fibrosis Foundation (CFF) accredited center if two mutations present or with a positive sweat test
Centers offer a multidisciplinary approach that includes:
MDs
RNs
Respiratory therapists
Dieticians
Social workers
Genetic counselors
A list of CFF-accredited centers in Indiana is included in this review
For a list of CFF-accredited centers in other states, please contact Constance Burrus at ISDH

19. Prognosis Average lifespan into the upper 30s
Progressive pulmonary disease is most common cause of death
Available therapies include nutritional, pulmonary, insulin, etc.
Gene therapy is not currently available clinically

20. Autosomal recessive inheritance

21. Recurrence risk (parents of child with CF)
For each pregnancy (same partner):
1 in 4 (25%) chance to have a child with CF
1 in 2 (50%) chance to have a child who is an asymptomatic carrier
1 in 4 (25%) chance to have a child who is neither affected with CF nor a carrier

22. Recurrence risk (cont.)
Each unaffected sibling of a child with CF has a 2/3 chance of being an asymptomatic carrier of a single CFTR mutation
Other family members are also at increased risk of being asymptomatic carriers
Carriers would have increased risk of having children with CF
Recommend genetic counseling / testing for at-risk family members

23. Future pregnancies (parents of a child with CF)
Prenatal genetic counseling* recommended for any couple concerned about the risk of having a child with CF
Prenatal screening for CF routinely offered to:
All Caucasian couples
Couples with family history of CF / CBAVD
*Contact ISDH for a list of prenatal genetic counselors & clinics in your area

24. For more information
If you would like to receive an electronic copy of this review, please contact:
Malorie Hensley, MS
Cystic Fibrosis Program Director
Indiana State Department of Health

25. For more information (cont.)
Malorie Hensley, MS
Cystic Fibrosis & Genomics Programs Director
Indiana State Department of Health
Courtney Eddy, MS, CGC, LGC, MT(ASCP)
INSTEP Director