Cystic fibrosis (CF), a monogenic disease, is the most common life-shortening autosomal recessive disease that afflicts people of Northern European descent. It was first formally reported to the worldwide medical community in 1949. According to the American Cystic Fibrosis Foundation patient registry, there are currently more than 30 000 CF patients in the United States and more than 70 000 CF patients throughout the world. Globally, about 1000 cases of CF are newly diagnosed every year, with over 75% of CF patients diagnosed at 2 years of age and an average age at diagnosis of about 3 years of age. CF incidence rates vary around the world, but rates as high as 1 in 2000 to 3000 live births are associated with Caucasian populations with Northern European ancestry. The median predicted survival time of CF patients in the United States is approximately 47.4 years (95% CI, 44.2-50.3) according to the Cystic Fibrosis Foundation 2018 Registry Report. However, epidemiological data on CF prevalence in China have not yet been reported, aside from observations that the genotypic spectrum of Chinese CF varies widely among resident subpopulations based on their geographical and ethnic origins.Numerous animal CF models have been established based on specific types of human CFTR mutations, but models differ in their effectiveness in mirroring features of human CF-specific disease.For example, the mouse CF model differs markedly from human CF at the pathological level, while at the molecular level CFTR genes of pig and human are highly homologous, but their corresponding CFTR protein structures and functions are vastly different. At present, ferret and rabbit CF models hold promise as human CF models, but additional models based on other species should also be evaluated.Meanwhile, the introduction of human CFTR genes harboring CFTR mutations into genomes of animals holds promise as a strategy for creating better animal models for human CF. Nevertheless, current animal models each have their own unique features that are useful for studying particular aspects of human CF disease, as described below.
Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 (GDF2)–related HHT diagnosed by genetic testing. A boy aged 5 years and 2 months presented with isolated hypoxemia. He was the product of a consanguineous marriage; his parents were second cousins. Physical examination revealed cyanosis of nail beds and clubbed fingers. Pulse oxygen saturation was 84% to 89%. Lung function, contrast-enhanced lung computed tomography, and noncontrast echocardiography were normal. A pulmonary perfusion scan revealed radioactivity in the brain and bilateral kidney, suggesting the existence of a intrapulmonary shunt. Whole-exome sequencing revealed a homozygous variant [c.1060_1062delinsAG (p.Tyr354ArgfsTer15)] in GDF2, which was found to be inherited from his heterozygous parents. At the age of 8 years, he developed epistaxis, and an angiogram revealed diffuse pulmonary arteriovenous malformations. At the age of 9 years, he was treated with sirolimus, and his condition improved significantly. However, his now 7-year-old sister with the same homozygous variant currently has no symptoms. Physical examinations revealed 1 pinpoint-sized telangiectasia on the chest of his mother and a vascular lesion on the forehead of his sister. Additionally, the patient’s father and great-uncle had a history of mild to moderate epistaxis. Mutation in GDF2 is a rare cause of HHT. Ours is the first report of homozygous GDF2-related HHT; in addition, this variant has not been reported previously. In our report, we also confirm variable expressivity, even with the same pathogenic variant in GDF2-related HHT.
Systemic inflammation mediated by LTs participates in the pathophysiological mechanisms of SDB in children. The magnitude of inflammation as reflected by urinary LTE(4) is significantly related to the severity of SDB and obesity. However, a correlation between LTE(4) concentration and adenotonsillar size is present only among nonobese children.
This report entails a case of refractory pneumonia with a wild variety of extra‐pulmonary manifestations due to macrolide‐resistant Mycoplasma pneumoniae infection in a 7‐year‐old boy. The diagnosis was based on isolating M. pneumoniae through cultivation from the patient's bronchial aspirations at admission and the following susceptibility testing. Initial treatments consisting of a combination of azithromycin and standard‐dosed methylprednisone (2 mg/kg) were completely nonresponsive and the patient's condition deteriorated rapidly. However, methylprednisone pulse therapy (20 mg/kg for 3 days, tapering within 1 month) and intravenous immunoglobulin (1 g/kg/day, two doses), in addition to moxifloxacin (10 mg/kg for 7 days) were remarkably effective and led to a favorable outcome without any observed side effects during inpatient hospitalization and outpatient follow‐up. Pediatr Pulmonol. 2013; 48:519–522. © 2012 Wiley Periodicals, Inc.
Objectives: To characterize the clinical and genotypic features of cystic fibrosisassociated pseudo-Bartter syndrome (CF-PBS) in Chinese children. Methods: We recruited and characterized the clinical manifestations of 12 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and Sanger sequencing validation were performed to define the genotypes. Results: CF-PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively), among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF-PBS was observed despite continued electrolyte supplementation during follow-up. In all, 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA [p.L88FfsX21], c.579+2insACAT, c.1210-3C>G, c.1733T>C[p.L578P], c.2236_2246del-GAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT [p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964-7A>G and ΔE23 [c.3718-? _3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin. Conclusions: In China, CF-PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF-PBS in school-going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin.
BackgroundMediastinal teratoma is uncommon in children. It can be very difficult to diagnose especially in early stage. Rarely, teratoma may rupture into adjacent structures and lead to lung lesions or pleuritis. The main rarity of our reported cases was the dynamic imaging findings very similar to the developmental process of tuberculosis in patients 1 and 2, the pachypleuritis in patients 2 and 3, the extremely elevated inflammatory markers very similar to empyema in patient 3, and the extremely atypical tumor shape in all patients.Case presentationWe present three pediatric patients presenting predominantly with recurrent hemoptysis and/or chest pain who were ultimately diagnosed with mediastinal teratoma containing pancreatic tissue. All three patients were initially suspected to have tuberculosis or empyema, and underwent relevant treatment, but without improvement. Patient 1 had left hilar enlargement, and subsequently an enlarging calcified cavity within high-density consolidation was identified. Patient 2 initially presented with right-sided pulmonary consolidation and pleuritis, and subsequently developed right lower lobe calcification, pleural thickening, and irregular soft tissue in the right inferior mediastinum. Patient 3 was initially found to have right lobe consolidation accompanied by a massive right-sided pleural effusion with extremely elevated inflammatory markers in serum and pleural effusion. The effusion later acquired heterogeneous density and appeared to become encapsulated. In patients 2 and 3, pleural biopsy identified fibrous tissue (with and without granuloma). Thoracotomy/thoracoscopy revealed mediastinal teratoma in each case, all of which were completely excised and the patients made uneventful recoveries. Histopathologic analysis revealed mature cystic-solid teratoma containing pancreatic tissue in all patients, and calcification in patients 1 and 2.ConclusionsClinicians should be mindful that mediastinal teratoma is a potential cause of hemoptysis, lung lesions and pleuritis. Calcification and pachypleuritis on chest imaging especially in patients without fever should be highly suspected of mediastinal teratoma. Pleural biopsy sometimes fails to assist in making a definitive diagnosis.
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