Cystic Fibrosis: A Review for Healthcare Providers

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Cystic FibrosisA Review for Healthcare Providers

• Provided by the Indiana State Department of Health

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Outline

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

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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
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Fast facts (cont.)
Frequency of CFTR mutations in ethnic groups 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 carries at least one CFTR mutation
African-Americans 1 in 65 carries at least one CFTR mutation
Genzyme Genetics, 2006
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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

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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

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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

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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)

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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

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What about children with one CFTR mutation?

• All children with at least one identified CFTR
  mutation should be referred for sweat chloride
  testing

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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

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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

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Features of CF

• Complex, multisystem disease
• Most commonly affects
• Respiratory system
• Gastrointestinal system
• Male reproductive system

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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

www.medicine.ufl.edu
www.nlm.nih.gov
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Gastrointestinal system

• Pancreatic insufficiency (gt 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)

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Male reproductive system

• gt 95 males with CF are infertile
• Abnormal development of Wolffian ducts leads to
  azoospermia
• Testicular development / function and
  spermatogenesis are usually normal

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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

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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

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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

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Autosomal recessive inheritance
www.search.com
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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

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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

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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
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CFF-accredited clinics in Indiana CFF-accredited clinics in Indiana CFF-accredited clinics in Indiana
Clinic name address Hours of operation Contact information
Riley Hospital for Children Wednesdays 10 am 5 pm 702 Barnhill Drive, ROC 4270 Indianapolis, IN 46202 317.274.7208
Deaconess Hospital Outreach Clinic During 4th week of month Monday, 840 am 430 pm Tuesday, 7 am 430 pm Wednesday, 7 11 am 4011 Gateway Boulevard Newburgh, Indiana 47630 812.450.3386
Lutheran Hospital Tuesdays and 3rd Wednesday of each month (times variable) 7950 W. Jefferson Boulevard Fort Wayne, IN 46804 260.435.7123
St. Joseph Regional Medical Center CF Pulmonary Disease Clinic 2nd and 4th Friday of each month 720 E. Cedar Street South Bend, IN 46617 574.239.6126
For a list of CFF-accredited centers in
neighboring states, please contact ISDH
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CFF-accredited sweat chloride testing laboratories in Indiana CFF-accredited sweat chloride testing laboratories in Indiana
Laboratory name address Contact information
Riley Hospital for Children 702 Barnhill Drive Indianapolis, IN 46202 317.274.1758
Deaconess Hospital 600 Mary Street Evansville, IN 47747 812.842.3880
Lutheran Hospital 7950 W. Jefferson Boulevard Fort Wayne, IN 46804 260.435.7123
South Bend Medical Foundation (provides testing for St. Joseph Hospital) 530 N. Lafayette Boulevard South Bend, IN 46601 574.234.4176
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For more information

• If you would like to receive an electronic copy
  of this review, please contact
• Constance Burrus, BS
• Cystic Fibrosis Coordinator
• Indiana State Department of Health
• 317.233.1292
• CBurrus_at_isdh.IN.gov

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For more information (cont.)

• Constance Burrus, BS
• Cystic Fibrosis Program Director
• Indiana State Department of Health
• 317.233.1292
• CBurrus_at_isdh.IN.gov
• Courtney Eddy, MT(ASCP), MS
• Genomics Program Director
• Indiana State Department of Health
• 317.233.9260
• CEddy_at_isdh.IN.gov