Clinical and laboratory profile of children with Cystic Fibrosis: Experience of a tertiary care center in Pakistan

Abstract

Objective:To determine the clinical presentation, diagnostic investigations and laboratory workup done in admitted children with cystic fibrosis at Aga Khan University Hospital Karachi, Pakistan.Methods:This is athree years retrospective study from January 2013 to December 2015 conducted at The Aga Khan University Hospital Karachi Pakistan, enrolling admitted patient from birth to 15 years of either gender, diagnosed with CF on the basis of clinical features and positive sweat chloride test. Different clinical presentations were noted including initial presentations. Sweat chloride values more than 60mmol/L were labeled as positive and consistent with diagnosis of CF. Available Delta F-508 mutation analyses were noted. Relevant laboratory and radiological investigations including sputum culture and HR-CT chest findings were documented. Results were analyzed using SPSS version 20.Results:Total 43 children were selected according to the inclusion criteria. Chronic cough (69.76%) was the most common initial clinical presentation. Mean age at onset of symptoms was 14.41± 26.18 months and mean age at diagnosis was 47.20 ± 45.80 months Respiratory features were most common in our cohort including chronic productive cough (90.71%), recurrent bronchopneumonia (72.09%) and asthma like presentation (44.19%) with wheezing and cough. 86% patients presented with failure to thrive. Gastroenterological features including steatorrhea were seen in 55.81% patients and 44.19% patients had abdominal distension. Mean sweat chloride value in our population was 82.70± 22.74. Gene analysis for Delta F-508 was identified in 12 (27.90%) patients. Bronchiectatic pulmonary changes on HRCT were seen in 18 patients (41.86%). Pseudomonas grew in 12 patients (27.90%) in sputum cultures at the time of diagnosis.Conclusion:Respiratory presentations predominate in CF children followed by gastrointestinal features. Nearly half of our patient had bronchiectatic changes on CT scan chest and more than quarter had pseudomonas colonization in the airways at the time of diagnosis. Delta F-508 mutation was found to be uncommon in our study population. There is significant delay in diagnosing patients with CF.

A comprehensive review of cystic fibrosis in Africa and Asia

“…Apart from c.1521_1523delCTT, a few other Western variants were also identified, although rare, except for c.350G>A which was found at 3.4%. ( Kabir et al, 2020 , Aziz et al, 2017 , Indika et al, 2019 ).…”

“…The second case was identified in a day-old infant enrolled in a pilot study for newborn screening in Nepal, who unfortunately did not survive beyond the third month. Based on the pilot study, the prevalence rate of CF in Nepal was 1 per 4360 live births ( Aziz et al, 2017 ).…”

“…Novel variants identified from this cohort include c.1002-7_1002-5delTTT, c.445G >T (p.Gly149Ter) and c.547C>A (p.Leu183Ile). More novel variants identified in Indian and Pakistani population include c.3986-3987delC, p.1792InsA, c.206T>A (p.Leu69His), c.473G>A (Ser158Asn), c.1478A >T (Gln493Leu), c.1507A>C (p.Ile503Leu), c.3985G>C (Glu1329Gln) and c.744-6del4 that represented 15% of the CF alleles ( Kabir et al, 2020 , Aziz et al, 2017 ). Variants c.1521_1523delCTT, and c.1647T>A were the most common variants in the Indian/Pakistan cohort at 17% and 5.7% respectively.…”

“… Ref. Country Nucleotide/“Variant cDNA name (Variant protein name) Legacy Name Eskandarani, 2002 Bahrain c.1161delC 1161delC Wei et al, 2020 , Indika et al, 2019 Pakistan c.1161delC 1161delC Mei-Zahav et al, 2005 , Alibakhshi et al, 2021 Sri Lanka c.1161delC 1161delC Rawashdeh and Manal, 2000 Jordan c.3670delA 3670delA Prasad et al, 2010 , Cui et al, 2020 , Liu et al, 2015 China c.3911T>G (p.Ile1304Arg) I1203R Mayer Lacrosniere et al, 2021 Democratic Republic of the Congo (c.399T>C (p.Thr133 = ) 399insT Prasad et al, 2010 , Cui et al, 2020 , Liu et al, 2015 China △E18-E20(c.2909-?_3367 +?del) (p.Gly980_Thr1112delinsGly) CFTR-dele18-20 Prasad et al, 2010 , Cui et al, 2020 , Liu et al, 2015 China △E7-E11(c.744-?_1584 +?del)(p.Arg248_Glu528delinsArgfsX) CFTR-dele7-11 Kabir et al, 2020 , Aziz et al, 2017 , Indika et al, 2019 India 1029del (p.Phe342_Cys343insTer) 1161delC (C343) Prasad et al, 2010 , Cui et al, 2020 , Liu et al, 2015 China 3G>A (p.Met1Ile) M1I Wang et al, 2019 , Teeratakulpisarn et al, 2006 , Lumpaopong et al, 2009 ...…”

Frequency of Cystic Fibrosis in Children with Recurrent Respiratory Infections by Sweat Chloride Testing: A Hospital-Based Cross-sectional Study

“…1 The common presenting symptoms and signs include persistent chest infections, pancreatic insufficiency, and raised sweat chloride levels. 2 However, many patients manifest mild or atypical symptoms and clinicians should be alert to suspect CF even when only a few of the typical features are present. 3 The classic or typical form of CF is diagnosed if a patient demonstrates clinical disease in one or more organ systems and has elevated sweat chloride levels (≥60 mmol/L).…”