Case Study by Gulnur Com , MD , 1 Lauren Willis , 2 Naga Jaya Smitha Yenduri , MD 3
Diagnosis of Cystic Fibrosis in the Era of Newborn Screening
Case Report
Until screening of newborns for cystic fibrosis ( CFNBS ) became available , diagnosis of cystic fibrosis ( CF ) relied on recognition of classical signs and symptoms . Widespread use of CFNBS and prenatal screening have resulted in diagnosis of CF early in life before symptoms are recognized . 1 On the other hand , there is a growing subset of individuals who did not undergo CFNBS and are receiving a diagnosis of CF during adulthood . This has been partially attributed to increased awareness of CF disease heterogeneity among physicians , widespread availability of cystic fibrosis transmembrane conductance regulator ( CFTR ) genotyping , and updated diagnostic criteria . 2 The CF Foundation Patient Registry reported that , in 2017 , only 58.4 % of 880 new CF patients were diagnosed via CFNBS . 3 However , symptomatic diagnosis of CF can be challenging due to subtle symptoms and incomplete clinical presentation . In individuals with residual function CFTR mutations , clinical manifestations of CF may develop later in life . 1 , 2 Here we report four individuals who were diagnosed with CF symptomatically by pediatric pulmonologists at Arkansas Children ’ s Hospital . Except for one patient , they were all born in the U . S ., and none of them underwent CFNBS . Although each of them had symptoms suggestive of CF , their diagnoses were delayed .
Case1
An 11-year-old male presented to the emergency department with respiratory failure requiring intubation and mechanical ventilation . He had been treated for asthma and had moderate obstructive pattern in his spirometry . He also had a history of nasal polypectomy at 7 and
1
Department of Pediatrics , Division of Pulmonology and Sleep Medicine , University of Florida , Studer Family Children ’ s Hospital , Pensacola , FL
2
Arkansas Children ’ s Hospital , Little Rock , AR
3
Texas Children ’ s Hospital-West Campus , Houston , TX
11 years of age . His sweat chloride was found to be 101 and 108 mmol / L Cl- and CFTR mutations were F508del / F508del . His fecal elastase level was 20 ug / g , consistent with pancreatic insufficiency ( PI ). His initial BMI was < 10th percentile and he required G tube placement . His respiratory cultures were positive for P . aeruginosa , and after treatment his best FEV1 improved to 70 % of predicted values .
Case 2
A 15-year-old female of Chinese descent was referred to the pulmonary clinic for recurrent sinus infections and chronic cough started at 5 years of age . The teen was born in China and the family migrated to the U . S . as a toddler .
When she was seen in the pulmonary clinic , her FEV1 was at 74 % of predicted , and her chest imaging showed mild bronchiectasis . CF diagnosis was confirmed with a sweat Cl- test ( 77 / 73 mmol / L ). She had normal pancreatic function . She had rare homozygous p . S492F mutations ( this mutation has not been reported before ). Since she was symptomatic and her respiratory cultures grew P aeruginosa , she was admitted to the hospital for IV antibiotic treatment . Following treatment , her best FEV1 remained in the mid 80 % of predicted values . Unfortunately , the family did not want to accept the diagnosis of CF , which resulted in poor adherence to medications and clinical appointments .
Case 3
A 19-year-old , Caucasian female presented with chronic cough unresponsive to inhaled corticosteroids . She worked as a pharmacy technician at a commercial pharmacy and was well known to have daily “ wet coughs .” She also had a history of recurrent pneumonia and sinus infections . She described loose stools since infancy , although her admission BMI was at 24 . Her initial FEV1 was 73 % of predicted and her sweat Cl- was 109 / 101 mmol / L on two occasions . She was found to be homozygous F508del with mutations and she had pancreatic insufficiency . Her respiratory cultures were positive for P . aeruginosa and after treatment , her FEV1 improved to mid- 80 % of predicted values .
Case 4
A 14-year-old , Caucasian male presented with chronic cough that had worsened over time . He had abnormal chest imaging showing diffuse bronchiectasis . His chronic cough had been attributed to asthma for years . His nutritional status was poor , with a BMI at the 10th percentile on presentation . He had significant clubbing and diffuse crackles on his chest exam .
Diagnosis of CF was confirmed with sweat Cl- levels of 101 and 93.6 . mmol / L . He was homozygous F508del with pancreatic insufficiency . His initial respiratory cultures were positive for P aeruginosa , and his initial FEV1 was 36 % of predicted . Following hospitalization and institution of CF targeted treatment , his best FEV1 improved to mid-50 % of predicted .
As seen in cases above , clinicians who are not experienced in CF likely expect that each CF patient should be presenting with failure to thrive , oily stools , barrel chest , clubbing , etc ., ( one size fits all ). However , some CF patients may present with subtle symptoms and findings and
222 • The Journal of the Arkansas Medical Society www . ArkMed . org