Transcript Cystic Fibrosis: A Review for Healthcare Providers

Cystic Fibrosis:
A Review for Healthcare Providers
Provided by the Indiana State Department of Health
Outline
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Fast facts about CF
Diagnosis
CFTR gene
Newborn screening
Symptoms
Medical management / prognosis
Inheritance / recurrence risks
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
Fast facts (cont.)
Frequency of CFTR mutations in ethnic groups*
Caucasians^
1 in 25
is the most common autosomal
recessive condition in Caucasians
carries at least one CFTR mutation
^CF
Hispanics
African-Americans
1 in 46
carries at least one CFTR mutation
1 in 65
carries at least one CFTR mutation
*Genzyme Genetics, 2006
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 46
common CFTR mutations
– Note: CF newborn screening does NOT test for all known
CFTR mutations
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
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
Why refer to CFF-accredited labs?
• Indiana has chosen to follow the national
precedent by referring patients to CFFaccredited centers for sweat chloride testing
and management
• CFF-accredited laboratories meet nationallyaccepted standards selected by the CFF in
conjunction with the Clinical and Laboratory
Standards Institute (CLSI, formerly NCCLS)
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 falsenegative rates
• Collection procedure is highly sensitive
• Other procedures are erroneous
What about children with one CFTR
mutation?
• All children with at least one
identified CFTR mutation should be
referred for sweat chloride testing
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
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
Features of CF
• Complex, multisystem
disease
• Most commonly affects:
– Respiratory system
– Gastrointestinal system
– Male reproductive system
Pulmonary system
• Chronic sinopulmonary disease
– Chronic cough / sputum production
– Wheezing
– Persistent infections with:
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www.medicine.ufl.edu
P. aeruginosa
S. aureus
H. influenzae
B. cepacia complex
– Abnormal chest X-rays
– Digital clubbing
www.nlm.nih.gov
Gastrointestinal system
• Pancreatic insufficiency (> 90% of patients)
• Malabsorption
– Especially of fats / fat-soluble vitamins
– May lead to failure to thrive, skin rashes, anemia
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Meconium ileus (15 – 20% of patients)
Pancreatitis
Hepatobiliary disease
Hypoproteinemia
Distal intestinal obstructions
CF-related diabetes (usually develops in teens)
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
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
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:
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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
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
Autosomal recessive inheritance
www.search.com
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
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 atrisk family members
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
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, 8:40 am – 4:30 pm
• Tuesday, 7 am – 4:30 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
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
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
[email protected]
For more information (cont.)
• Constance Burrus, BS
Cystic Fibrosis Coordinator
Indiana State Department of Health
317.233.1292
[email protected]
• Courtney Eddy, MT(ASCP), MS
Genetics Specialist
Indiana State Department of Health
317.233.9260
[email protected]