1/109. Pitfall in the use of genotype analysis as the sole diagnostic criterion for cystic fibrosis.In this report, we present an asymptomatic infant, seen for a second opinion, who was given the diagnosis of cystic fibrosis (CF) as a neonate based on the presence of two mutant alleles, DeltaF508 and R117H. The diagnosis of CF adversely affected the family's emotional, employment, and financial statuses. Our evaluation included sweat chloride, nasal transepithelial potential difference, and bronchoscopy with bronchoalveolar lavage measurements, all which were consistent with findings expected from an individual without CF. genotype analysis for the sequence polymorphism in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene revealed the 7 thymidines and 9 thymidines alleles. We conclude that this patient probably expresses enough epithelial cell surface CFTR function such that she has a normal phenotype. Based on our evaluation, she does not meet the current diagnostic criteria for CF. Although genotype analysis can be an useful adjunct, it should not be the sole diagnostic criterion for CF.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
2/109. Combined lung and liver transplantation in a girl with cystic fibrosis.PURPOSE: To describe the anesthetic considerations of a combined lung and liver transplant in a 14-yr-old girl with cystic fibrosis. CLINICAL FEATURES: A 14 yr-old girl with cystic fibrosis presented for combined liver and lung transplantation. Anesthetic management was complex in that the pulmonary, hemodynamic, and hematological changes after cardiopulmonary bypass and lung transplantation made the management of the subsequent liver transplant unique. We used a moderate dose fentanyl and isoflurane anesthetic with invasive monitoring including a pulmonary artery catheter. Upon reperfusion of the new liver our patient exhibited severe pulmonary hypertension that was associated with a decrease in cardiac output and systemic hypotension. Utilizing a pulmonary artery catheter, this episode was treated with an increase of prostaglandin E1 (PGE1) infusion to 0.025 microg x kg(-1) x min(-1) and the initiation of 3 microg x kg(-1) x min(-1) dobutamine. The pulmonary hypertension resolved and the cardiac output and blood pressure returned to baseline levels. CONCLUSION: The anesthetic considerations for a combined lung and liver transplant are complex because of the interactions and alterations in cardiovascular, pulmonary and hemostatic systems. The use of a pulmonary artery catheter was critical to the management of our patient because it allowed us to accurately treat an episode of hypotension occurring during liver transplantation. This episode was secondary to acute pulmonary hypertension which is common after pulmonary transplantation but unusual during liver transplantation. It is also critical that a team approach is used to consider all of the concerns of the multiple services managing these complex patients.- - - - - - - - - - ranking = 0.00016298224103965keywords = gland (Clic here for more details about this article) |
3/109. Two novel mutations in a cystic fibrosis patient of Chinese origin.Cystic fibrosis is rare in non-Caucasian populations, and in such populations little is known about the spectrum of mutations and polymorphisms in the CFTR gene. We studied a 23-year-old patient of Chinese ethnicity with sweat chloride values of 104 mM/l, pancreatic sufficiency, an FEV1 60% of normal, sputum cultures positive for staphylococcus aureus and burkholderia cepacia, and a history of allergic bronchopulmonary aspergillosis. Genetic screening for 31 common CFTR mutations was negative, leading us to search for unknown mutations using single-strand conformation polymorphism and heteroduplex analysis (SSCP/HA). Two novel mutations were detected. In exon 4, a deletion of 8 bp (451458, deltaGCTTCCTA) causes a frameshift and immediately creates a stop codon. In exon 16, mutation 3041G-->A causes the missense change G970D. Functional analysis using an isotopic flux assay indicated that the G970D mutation retains partial function; western blotting indicated that the protein is glycosylated. The patient is heterozygous for the common polymorphisms (2694T/G) in exon 14a and (GATT)6/7 in intron 6a, indicating that these variants arose in ancestors common to Caucasians and Chinese.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
4/109. Identification of novel mutations of the CFTR gene in a Japanese patient with cystic fibrosis.Cystic fibrosis (CF) is an inheritable disorder characterized by defective epithelial chloride transport and progressive lung disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The subject of this study was an 8-year old Japanese boy, who developed typical CF symptoms including meconium ileus, pancreatic insufficiency, an elevated sweat chloride concentration and pulmonary disease. Analysis of the CFTR gene of this patient revealed compound heterozygous mutations in exon 11 (1742 delAC) and intron 9 (1525-18 GtoA) of the CFTR gene.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
5/109. Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.An infant with cystic fibrosis and her asthmatic father were diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA). Cystic fibrosis was diagnosed in the infant at 6 weeks of age, and gene mutations were W1282X/G542X. She was diagnosed definitively as suffering from ABPA at age 3.5 years, but had suggestive symptoms from age 11 months. This may be the youngest age described to date for ABPA. The child responded well to systemic steroid therapy, but remained steroid-dependent over the next 4 years. Treatment with itraconazole enabled a marked reduction in steroid dosage. The father was an asthmatic, and a heterozygote for the cystic fibrosis transmembrane regulator (CFTR) mutation W1282X. He had a normal sweat test, atopy, and moderate reversible airway obstruction. There was no proven exposure to aspergillus in the home environment. The importance of considering the diagnosis of ABPA even in infancy, the therapeutic dilemmas, and the possible role of abnormal CFTR function in the development of ABPA are discussed.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
6/109. Case report of a Thai male cystic fibrosis patinet with the 1898 1G-->T splicing mutation in the CFTR gene: a review of East Asian cases. Mutations in brief no. 196. Online.Cystic fibrosis (CF) is the most common fatal autosomal recessive multisystem disorder, which occurs mainly in European-derived populations. The incidence of CF varies between 1 in 2000 to 3000 live-births in various ethnic groups. The disease is rare in East Asians. Here we report a 9 year old Thai male patient, who was diagnosed to have CF based on recurrent pneumonia, a slow weight gain, pancreatic insufficiency and repeatedly elevated sweat chloride levels by two different methods. A comprehensive genetic analysis showed the splicing mutation, 1898 1G-->T, which was apparently of maternal origin. literature search found 39 documented cases of CF patients in East Asians. CFTR (MIM# 602421) genotyping was performed in 14 patients including our patient and in 9 of them a CF allele was identified. The findings seem to indicate that the splicing mutations, 1898 1G-->T and 1898 5G-->T are more common in East Asian CF patients.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
7/109. Triple A syndrome mimicking cystic fibrosis.We report a 2-8/12 year-old male who presented with symptoms resembling cystic fibrosis (failure to thrive, developmental delay and recurrent diarrhea) and had elevated sweat chloride concentration. Mucosal hyperpigmentation led to the diagnosis of adrenal insufficiency which was ultimately shown to be a component of triple A syndrome (achalasia, alacrima, adrenal insufficiency). Elevated sweat chloride concentration normalized after initiation of adrenal replacement therapy. We suggest that non-CF conditions causing elevated sweat chloride concentration should be considered in patients with atypical findings or who do not have objective evidence of pulmonary or exocrine pancreatic disease.- - - - - - - - - - ranking = 3keywords = sweat (Clic here for more details about this article) |
8/109. Reaching the diagnosis of cystic fibrosis--the limits of the spectrum.BACKGROUND: Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in Caucasians. Typically it is a multisystem disease diagnosed by increased chloride levels on sweat testing, with mortality due mainly to progressive respiratory disease. The clinical spectrum of CF has recently been much expanded. genetic testing for mutant CF transmembrane regulator has revealed atypical cases where sweat test results are borderline or normal. In other patients, genetic mutations cannot be identified but abnormal CFTR function is shown using nasal potential difference measurement. OBJECTIVES: To highlight the diagnostic and therapeutic dilemmas in cases of atypical cystic fibrosis. methods: We reviewed patients with atypical CF and widely varying phenotype who are managed at Schneider Children's Medical Center of israel. RESULTS: Two patients had severe lung disease but little expression in other organs. Accurate diagnosis was essential to enable aggressive therapy in a specialized center. Four other patients are in excellent general health but have symptoms limited to male infertility, heat exhaustion, pancreatitis or transient liver dysfunction, while lung disease is minimal. For these patients, careful counseling is needed to avoid unnecessary upheaval, inappropriately aggressive management, and the psychosocial implications of a CF diagnosis. These dilemmas have increased considerably in our center, as in others worldwide. CONCLUSION: It is our obligation as clinicians--at the level of both primary physician and referral center--to maintain an ever higher index of suspicion for CF, tempered by a rational program of counseling and management appropriate to the individual.- - - - - - - - - - ranking = 2keywords = sweat (Clic here for more details about this article) |
9/109. Protracted neonatal hypertrypsinogenaemia, normal sweat chloride, and cystic fibrosis.The cystic fibrosis (CF) clinical spectrum has greatly expanded in the past few years, including atypical forms with low sweat chloride concentrations. Two cases are presented which suggest that children detected by neonatal CF screening whose trypsinogen concentrations are still raised by the second month of age could, despite a negative sweat test, be affected by an atypical CF with fully expressed pulmonary involvement.- - - - - - - - - - ranking = 6keywords = sweat (Clic here for more details about this article) |
10/109. Novel cystic fibrosis mutation (2215insG) in two adolescent Taiwanese siblings.Cystic fibrosis (CF) is an autosomal recessive disorder that is rarely found in Asians. Only four cases of CF from four different families have been reported in taiwan. We report two cases of CF involving two teenage siblings. Both presented with repeated airway infections, poor weight gain, clubbing of the fingers, hypoxemia, and obstructive ventilatory impairment. Multiple focal bronchiectases and emphysema were demonstrated on high-resolution computed tomography. sweat chloride concentrations, as measured using the modified sweat chloride test in a closed space with a heater, were 327 mmol/L and 276 mmol/L, respectively. To confirm the CF diagnosis, dna mutation analysis was performed. All 27 exons of the CF transmembrane conductance regulator (TR) gene and their flanking intron sequences were screened for nucleotide sequence alterations, and the mutations were then identified by direct dna sequence analysis. Both siblings carried 1898 5G-->T; a mutation previously identified in taiwan. In addition, the mutation analysis identified a new single-base-insertion mutation in exon 13 on the second CFTR allele of these patients. This mutation, named 2215insG, is expected to cause a significant disruption of CFTR function. The 1898 5G-->T/2215insG genotype is thus consistent with the CF diagnosis. A new missense mutation, S895N, in exon 15 of the CFTR gene, which cosegregated with 2215insG, was also identified in both of these patients.- - - - - - - - - - ranking = 1keywords = sweat (Clic here for more details about this article) |
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