Table 1 : Demographics and Clinical Features of Individuals Diagnosed with CF Symptomatically Late in Life
Case |
Diagnosis Prior to CF |
Age of Dx ( years ) |
Ethnicity |
CFTR Mutation |
Sweat Cl |
|
|
Level |
|
Initial Presentation |
Pancreas Status |
FEV1 at Diagnosis |
# 1 Asthma , Nasal polyps |
11 |
Caucasian |
Homozygous |
|
|
F508del |
|
|
( pPhe508del ) |
|
101 / 108 Mmol / L |
Respiratory failure , nutritional failure |
Insufficient |
N / A Respiratory failure |
# 2 |
Asthma |
15 |
Chinese |
Homozygous |
|
|
|
|
p . S492F |
|
77 / 73 Mmol / L |
Cough , recurrent sinus infection
Cough , sputum production , GI symptoms
|
Sufficient |
74 % p |
# 3 Recurrent pneumonia , Sinusitis , Asthma |
19 |
Caucasian |
Homozygous |
|
|
F508del |
|
|
( pPhe508del ) |
|
109 / 101 Mmol / L |
|
Insufficient |
73 % p |
# 4 Chronic cough |
14 |
Caucasian |
Homozygous |
|
|
F508del |
|
|
( pPhe508del ) |
|
93 / 101 Mmol / L |
Respiratory distress , chronic cough , poor nutrition |
Insufficient |
36 % p |
Terminology
In attempts to differentiate the wide-spectrum clinical CF phenotypes , there have been various definitions proposed , including severe CF , mild CF , atypical CF , or classic / non-classic CF . In addition , there have been new / evolving definitions related to CFNBS , such as CF- TR-related metabolic syndrome referring to inconclusive diagnosis following CF- NBS ( in the U . S .) and CF screen positive , an inconclusive diagnosis ( in Europe ). Finally , CFTR-related disorder refers to an entity with single organ / system involvement such as congenital bilateral absence of the vas deferens , pancreatitis , or bronchiectasis associated with CFTR dysfunction that does not fulfill the diagnostic criteria for CF 1 , 9
False Negative Screening
CFNBS is complex and is not perfect ; therefore , false negative results may occur . There are many potential reasons for a false negative screening including , but not limited to , unacceptable specimen quality , specimen labeling errors , and inappropriate testing cutoff value . Therefore , clinicians should be aware that a child can have CF despite negative NBS . 10
Conclusion
CF diagnosis can be challenging in nonscreened and screened populations .
Severity of CF symptoms may be different even in siblings with the same CFTR mutations . Since nationwide CFNBS was implemented only recently in the U . S . and many individuals born prior to 2010 have not been screened , CF should be considered in individuals who present with symptoms suggestive of the disease . CFNBS is complex and is not perfect . Even after a negative screening , clinicians should maintain a high index of suspicion of CF . The terminology related to CFNBS is confusing and clinicians should work with CF specialists to communicate with their families after positive screening .
References
1 . Sosnay PR , White TB , Farrell PM , et al . diagnosis of Cystic fibrosis in Nonscreened Populations . J Pediatr . 2017 ; 181S : S52-S57 .
2 . Desai S , Wong H , Sykes J ., et al . Clinical Characteristics and Predictors of Reduced Survival for Adult-diagnosed Cystic Fibrosis . Analysis of the Canadian CF Registry . Ann Am Thorac Soc . 2018 Oct ; 15:1177-1185 .
3 . Cystic Fibrosis Foundation Patient Registry 2017 Annual Data Report Bethesda , Maryland © 2018 Cystic Fibrosis Foundation
4 . De Boeck K , Amaral MD . Progress in therapies for cystic fibrosis . Lancet
Respir Med 2016 ; 4:662-674 . 5 . Boyle M P . Strategies for Identifying Modifier Genes in Cystic Fibrosis . Proc Am Thorac Soc . 2007 ; 4 : 52 – 57 , 2007
6 . Glasgow AMA , De Santi C , Greene CM . Non coding RNA in cystic fibrosis . Biochem Soc Trans . 2018 ; 46:619-630
7 . Philip M . Farrell PM , White TB , Clement RL , et al . Diagnosis of Cystic Fibrosis : Consensus Guidelines from the Cystic Fibrosis Foundation . J Pediatr . 2017 ; 181S : S4-1
8 . Zheng B , and Ling Cao L . Differences in Gene Mutations Between Chinese and Caucasian Cystic Fibrosis Patients . Pediatr Pulmonol . 2017 ; 52 : E11-14
9 . Clement RL , Borowitz D S , Gonska T , et al . Cystic Fibrosis Transmembrane Conductance Regulator-Related Metabolic Syndrome and Cystic Fibrosis Screen Positive Inconclusive Diagnosis . J Pediatr 2017 ; 181S : S45-51
10 . Edmondson C , Grime C , Prasad A , et al . Cystic fibrosis newborn screening : outcome of infants with normal sweat tests . Arch Dis Child 2018 ; 103:753 – 756 .
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