Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.
Alkalosis ; complications ; Bartter Syndrome ; China ; Cystic Fibrosis ; diagnosis ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; Diagnosis, Differential ; Exome ; Female ; Humans ; Hypokalemia ; complications ; Infant ; Male ; Mutation

Cystic fibrosis (CF) is an autosomal recessive disease that is very rare in Asians: only a few cases have been reported in Korea. We treated a female infant with CF who had steatorrhea and failure to thrive. Her sweat chloride concentration was 102.0 mM/L. Genetic analysis identified two novel mutations including a splice site mutation (c.1766+2T>C) and a frameshift mutation (c.3908dupA; Asn1303LysfsX6). Pancreatic enzyme replacement and fat-soluble vitamin supplementation enabled the patient to get a catch-up growth. This is the first report of a Korean patient with CF demonstrating pancreatic insufficiency. CF should therefore be considered in the differential diagnosis of infants with steatorrhea and failure to thrive.
Alternative Splicing ; Base Sequence ; Cystic Fibrosis/complications/diagnosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Diagnosis, Differential ; Exocrine Pancreatic Insufficiency/complications/diagnosis/*genetics ; Female ; Frameshift Mutation ; Humans ; Infant ; Republic of Korea ; Steatorrhea/diagnosis

OBJECTIVECystic fibrosis (CF) is rare in Chinese mainland. We present two cases of CF patients diagnosed by gene analysis. Their clinical manifestations and genetic mutation features are analyzed in this article. It will be of special interest to pediatricians in recognition of CF.

METHODThe clinical material of two CF patients who were diagnosed by gene analysis was retrospectively analyzed.

RESULTThe first patient is a 13-year-old girl. She had a complaint of recurrent fever and cough for 6 months, expectoration for 2 months and hemoptysis for 20 days. After 3 months of her birth, she was operated on for bullae of lung. She was susceptible to upper respiratory tract infection. There was no family history of recurrent wheeze and other special diseases. Aspergillus fumigatus specific IgE was at grade 3 and aspergillus fumigatus IgG was high. Pseudomonas aeruginosa was positive in sputum culture. Sweat testing was performed and Na+ was higher. Pulmonary CT indicated bronchiectasis. Nasal sinus CT showed optical density of soft tissue within maxillary sinus and chronic bilateral sinusitis. The electron microscopy of cilia suggested immobile cilia syndrome. A heterozygotic mutation (263T > G, 2909G > A) was found after CFTR genetic mutation analysis. Both her parents were carriers. She was treated with inhalation of nebulized hypertonic saline and postural drainage for a long time. And she got better during a follow up period of 1 year. The second patient was a 10-year-old girl who complained of recurrent expectoration for 3 years and shortness of breath for half a year. She had a history of sinusitis and steatorrhea. The family history was normal. Both the lipase and insulin level in blood serum was lower.Pseudomonas aerugino and Aspergillus fumigatus were both positive in sputum culture. Aspergillus fumigatus IgE was normal. Pulmonary CT indicated bronchiolitis and bronchiectasis. Nasal sinus CT showed bilateral maxillary sinusitis. CFTR genetic mutation analysis revealed a homozygous mutation (3196C > T). Her parents and relatives did not participate in this study. Unfortunately, this child died of respiratory failure 3 months after discharge.

CONCLUSIONCFTR gene mutation was a main cause of CF. Common symptoms are those of bronchiectasis, pancreatitis and sinusitis. The two Chinese patients were diagnosed by gene analysis. One had a heterozygous mutation (263T > G, 2909G > A) and the other had a homozygous mutation (3196C > T), not ΔF508 which is common in western countries.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Bronchiectasis ; etiology ; genetics ; Child ; Cystic Fibrosis ; complications ; diagnosis ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; DNA Mutational Analysis ; Female ; Heterozygote ; Homozygote ; Humans ; Mutation ; Retrospective Studies ; Sinusitis ; etiology ; genetics