Transcript CF or CRMS, What is the Difference?, Jackie Zirbes, RN, PNP

March 7, 2015
CF or CRMS
What is the Difference ?
Jacquelyn M Zirbes, DNP
Adult Diagnosis
 Clinical
 Sweat
 Or
disease
Chloride > 60 mmol/L *
Intermediate Range of 40-59mmol/L
 And
2 CFTR Gene Mutations identified
Cystic Fibrosis in the
Adult/Adolescent

• Allergic bronchopulmonary aspergillosis

• Chronic pansinusitis or nasal polyposis

• Bronchiectasis

• Haemoptysis

• Idiopathic recurrent pancreatitis

• Portal hypertension

• Delayed puberty

• Azoospermia secondary to congenital
bilateral absence of the vas deferens
Classic CF Characteristics
 Chronic
Sinopulmonary Disease
 Characteristic
 Nutritional
 Salt
GI abnormalities
Abnormalities
Loss
 Male
Genital abnormalities resulting a
azoospermia
Sinus Disease
Health Lung
CF Lung Disease
Gastrointestinal Abnormalities
Nutritional Needs
Male Azoospermia
The Younger Age Group
Classic Signs and Symptoms
 Neonatal
 Infancy
 Meconium
ileus

Chest xray

FTT
jaundice

Low Protein
 Abdominal

Chronic Diarrhea
 Intestinal

ABD Distension

Cholestasis

S.a. Pneumonia

Vit A & E deficiency
 Protracted
atresia
The Word: The Initials
 CRMS=
 CFTR-Related
 Cystic
Metabolic Syndrome=
Fibrosis Transmembrane
Conductance Regulator Protein Related
Metabolic Disorder
The Adult
 Older
individuals with sweat chloride < 60
and combination of mutations have been
characterized as ‘‘atypical CF,’’ ‘‘nonclassical CF,’’ ‘‘CFTR-related disorders,’’
‘‘low-risk genotype,’’ or ‘‘mild variant CF,’’
 But
the adults now present for diagnostic
evaluation because of signs or symptoms,
whereas infants identified by CF NBS are
symptom free.
The Adult
What is CRMS
 High
IRT on NBS
 Sweat
chloride values <60 mmol/L And
 Up
to 2 CFTR mutations, at least 1 of which
is not clearly categorized as a “CF disease
causing mutation”
 No
multi-organ symptoms of cystic fibrosis
 Does
not imply CF is present at this time
Newborn Screening
CRMS and NBS
Step 1: IRT testing
NBS State Laboratories
< 98.4%ile
Screen Negative
≥ 98.4%ile
High IRT
Step 2: CFTR mutation
testing at Stanford University
(40 mutations panel)
No mutations
Screen Negative
2 mutations
Screen Positive
1 mutation
Indeterminate
Step 3: DNA Scanning and
Focused sequencing
Stanford University
2 mutations/variants
Screen Positive
Step 4:Referral to CF
Center
1 mutation
Carrier
Genetic Counseling
Services Offered
CFTR2 Reference
http://www.cftr2.org
CFTR and Sweat Chloride
Sullivan & Freedman, 2009
CRMS in Infants
 Milder
clinical course than CF
 Pancreatic
Sufficient
 Well
nourished, do not require PERT or
caloric supplements
 CF
pseudomonas>CRMS pseudomonas
 Some
Ren, et. al 2010
individuals do develop CF disease
Recommendation CRMS
 Genetic
 Refer
concepts and formal counseling
to correct resources
 Explain
difference between CF and CRMS
 Uncertainty
 Full
of Prognosis
Life expectancy
 CRMS
symptoms DO need to be treated
 Baseline
and ongoing follow-up with
monitoring plan
Recommendations Continues

Repeat sweat chloride at 6 months

Symptom free infants twice yearly visits during first
year then once yearly.

Oropharyngeal culture with every visit

X-rays if symptomatic– airway clearance if signs

Spirometry when able

Smoke free environment

Influenza vaccine
Recap of CRMS
 High
IRT on NBS
 Sweat
chloride values <60 mmol/L And
 Up
to 2 CFTR mutations, at least 1 of which
is not clearly categorized as a “CF disease
causing mutation”
 No
multi-organ symptoms of cystic fibrosis
 Does
not imply CF is present at this time
Consensus

Phenotype more important than genotype

CFF recommends genetic counselor discussion

Communication with primary care to concurrently provide
care

Many infants with CRMS will be healthy during early
childhood

Male higher risk of infertility

Benefit from new treatments

Update families as information becomes available

Treat P aeruginosa.

Research biomarkers and identification of genetic modifier
to help with more accurate prognosis
References

Borowitz, D., Robinson, K., Rosenfeld, M., Davis, S., Sabadosa, K., Spear, S.,
Michel, S. Parad, R., White, T., Farrell, P., Marshall, B., Accurso, F. (2009). Cystic
Fibrosis Foundation evidence-based guidelines for management of infants with
cystic fibrosis. Journal of Pediatrics, 155, 6, suppl.4, 73-93.

Borowitz, D., Parad, R., Sharp, J., Sabadosa, K., Robinson, K., Rock, M., Farrell, P.,
Sontag, M., Rosenfeld, M. Davis, S., Marshall, B., & Accurso, F. (2009). Cystic
Fibrosis Foundation Practice Guidelines for the management of infants with
cystic fibrosis transmembrane conductance regulator-related metabolic
syndrome during the first two years of life and beyond. Journal of Pediatrics:
155: S106-16.

Castellani, C., Cuppens, H., Macek, M. Jr., Cassiman J., Kerem E., Durie, P., et al.
(2008) Consensus on the use and interpretation of cystic fibrosis mutation
analysis in clinical practice. Journal of Cystic Fibrosis: 7: 179-96.

Farrell, P., Rosenstein, B., White, T., Accurso, F., Castellani, C., Cutting G., et al.
(2008) Guidelines for diagnosis of cystic fibrosis in newborns through older adults:
Cystic Fibrosis Foundation consensus report. Journal of Pediatrics,: 153: S4-14.

Feldmann, D., Couderc, R., Audrezet, M., Ferec, C., Bienvenu, t., Desgeorges,
M., et al. (2003) CFTR genotypes in patients with normal or borderline sweat
chloride levels. Human Mutation, 22: 340.
References continued

O’Connor GT, Quinton HB, Kahn R, et al.; ( 2002). Northern New England Cystic
Fibrosis Consortium .Case-mix adjustment for evaluation of mortality in cystic
fibrosis. Pediatric Pulmonology, ;33(2):99-105.

O’Connor GT, Marshall, B, Quinton H, et al.( 2006). Public Reporting of Cystic
Fibrosis Outcomes: Methods for Case-Mix Adjustment [abstract]. Pediatric
Pulmonology - Supplement.;29S:119-120.

O’Sullivan, B. & Freedman, S. (2009). Cystic Fibrosis. The Lancet, 373, 1891-1904

Sosnay PR. Siklosi KR. Van Goor F. Kaniecki K. Yu H. Sharma N. Ramalho AS.
Amaral MD. Dorfman R. Zielenski J. Masica DL. Karchin R. Millen L. Thomas PJ.
Patrinos GP. Corey M. Lewis MH. Rommens JM. Castellani C. Penland CM.
Cutting GR. (2013). Defining the disease liability of variants in the cystic fibrosis
transmembrane conductance regulator gene. Nature Genetics. 45(10):1160-7.

Watts KD, Seshadri R, Sullivan C, McColley, SA. (2009) Increased prevalence of
risk factors for morbidity and mortality in the US Hispanic CF population.
Pediatric Pulmonology ;44(6):594-601.

Watts, K.& Schechter, M. (2010). Origins of outcome disparities in pediatric
respiratory disease. Pediatric Annals, 39: 12, 793-799. doi: 10.3928/0090448120101116-10
“The prevention of disease today is one of
the most important factors in line of
human endeavor.”
Charles Mayo, 1913
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Questions and Discussion