Multicenter Surveillance of Cystic Fibrosis in Korean Children

Abstract

Purpose Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, is rare among non-Caucasians. We aimed to identify the clinical features and CFTR mutations in Korean children. Methods We included 18 pediatric patients with CF diagnosed using sweat chloride test or genetic analysis for 30 years. HEK293 cells were transfected with wild-type CFTR , ΔF508- CFTR , and L441P- CFTR mutant plasmids for 24 hours and treated with CFTR correctors (VX809 and VX661). Results The median age at diagnosis was 9.2 years. Eleven patients had growth retardation, and 6 had a respiratory failure at diagnosis. Genetic analysis was used for all patients, while sweat testing was for 8 patients. At diagnosis, the median z scores of forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, and forced expiratory flow at 25%–75% of forced vital capacity were −3.61 (−5.78, 1.78), −3.38 (−4.40, −0.60), and −4.45 (−5.78, 0.54), respectively. Two patients were treated with dornase alfa and only one with CFTR modulator. Patients were followed up for 3.7 years as a median. Four patients died at 10.6 years, with 4.2 years of post-diagnosis survival. The most common mutation was exon 16-17b deletion (19.4%). Among 11 single nucleotide variants, c.1322T>C (p.Leu441Pro, L441P) was detected in 4 patients. In the functional assay, L441P-CFTR correction was well restored by CFTR correctors compared with ΔF508. Conclusions CF is extremely rare in Korean children and is caused by different mutations from those commonly observed in Caucasians. Early diagnosis and treatment availability may improve outcomes. CFTR modulators may be effective for Asian patients with rare CFTR mutations, c.1322T>C (p.Leu441Pro).

Primary Ciliary Dyskinesia: A More Prevalent Disease Than Previously Believed?

“…CF was also diagnosed at a later age in Korea compared to Western countries due to limited awareness and diagnostic tools. 9 These multicenter surveillances, including the current study by Kim et al ., 7 assist Korean physicians in comprehending the clinical features of patients with rare diseases, thereby facilitating early diagnosis and treatment. Especially, PCD could be more prevalent than previously believed because of a lack of awareness, given the advancements in our understanding of ciliopathies and the potential role of genetic testing in future diagnostic procedures.…”

A Case Report of the First Filipino Infant Diagnosed with Cystic Fibrosis through the Philippine Newborn Screening Program

“…Reports from Japan, China, Jordan, and Bahrain have demonstrated prevalences of 1:350,000, 1:153,825, 1:2,500 and 1:5,000, respectively, demonstrating a wide variability among different Asian subgroups. [1][2][3] Genetics may be the cause of this variability since even in the United States, prevalences among different ethnic populations differ wherein prevalences show 1:3,200 among Caucasians, 1:10,000 among Hispanics, 1:10,500 among Native Americans, 1:15,000 among African Americans, and 1:30,000 among Asian Americans. 2 While Philippine prevalences on CF is unknown, five Filipinos have previously been diagnosed through the California Newborn Screening Program in the United States.…”

“…[1][2][3] Genetics may be the cause of this variability since even in the United States, prevalences among different ethnic populations differ wherein prevalences show 1:3,200 among Caucasians, 1:10,000 among Hispanics, 1:10,500 among Native Americans, 1:15,000 among African Americans, and 1:30,000 among Asian Americans. 2 While Philippine prevalences on CF is unknown, five Filipinos have previously been diagnosed through the California Newborn Screening Program in the United States. 4 The differences in prevalences imply that genetic differences play a significant role in this disease occurrence in different populations.…”

Clinical and Imaging Features of Cystic Fibrosis in Korean Children

“…In Korea, only 23 cases of CF have been reported, and the median age of diagnosis was 4.5 years, which is higher than those reported in Western populations (median age at diagnosis: 6 months) ( 5 6 ). Most Korean patients present with respiratory symptoms ( 7 ). Meconium ileus and pancreatic insufficiency were reported in 47.8% and 57.9% of patients, respectively ( 6 ) which were lower than those in Western populations, where pancreatic insufficiency is reported in 80% of the patients, suggesting possible differences in clinical symptoms based on ethnicity and geography ( 6 8 ).…”