Clinical complications in children with false-negative results in cystic fibrosis newborn screening

Abstract Objective: To present signs and symptoms and clinical course in cystic fibrosis patients with false-negative newborn screening (CF NBS). Materials and methods: All children presented in this paper were covered by CF NBS. The group of 1.869.246 newborns was screened in the Institute of Mother and Child in Warsaw within a period of 01.01.1999 - 31.05.2019. Screening protocols evolved over time from IRT/IRTto IRT/DNA/EGA. Results: The authors identified 11 patients with false-negative NBS, in whom CF was diagnosed based on clinical symptoms or the examination of siblings with positive CF NBS. In the study group, the diagnosis was made significantly later in comparison to positive CF NBS patients ranging from 2 months to 15 years of age. CF NBS strategy does not significantly affect the sensitivity of the screening. Conclusion: In the presence of clinical symptoms, additional diagnostics must be implemented, in spite of the negative screening results. At first, the sweat test should be conducted, followed by a DNA analysis of the most common mutations in the given population. The diagnostic process requires searching for CFTR mutations not typically associated with a high chloride concentration in sweat. Repetition of sweat chloride concentration enables the diagnosis in children whose initial chloride values in sweat are borderline, and no CF-causing mutations are detected. In strong clinical indications, the extension of DNA analysis (EGA) is recommended in order to identify rare CF variants. In children with meconium ileus, genetic analysis is mandatory.

Mutational Spectrum of the CFTR Gene in the Kazakhstan Population

Objective: To study the frequency and spectrum of CFTR gene variants in different ethnic groups of Kazakhstan. Methods: We reviewed the records of 58 patients with cystic fibrosis. All the patients underwent molecular genetic analysis to reveal genotype-phenotype correlations. Results: The median (IQR) age of the patients was 5.4 year (7 months, 18 year); 40% were diagnosed at the age of 5-10 year. The study identified 28 specific variants: p.Phe508del, the variant most common in the European population, was detected in 30 patients (51.7%). Variants other than p.Phe508del were revealed in 31% (21 patients). Conclusions: We found a number of specific variants characteristic of the Kazakhstani population. A pronounced regression of disease symptoms was detected in patients with mild mutations; whereas in patients with severe mutations, therapy produced very little effect.

A influência da idade e do genótipo sobre os níveis de cloreto do suor em uma população pediátrica com fibrose cística no estado da Bahia / The influence of age and genotype on sweat chloride levels in a pediatric population with cystic fibrosis in the state of Bahia

Introdução: a fibrose cística é a doença autossômica recessiva mais comum em populações caucasianas e a sua etiologia está associada a variantes patogênicas no gene CFTR. O teste do suor é considerado o padrão ouro para o diagnóstico dessa enfermidade. Estudos apontam que o genótipo do CFTR e a idade dos indivíduos influenciam as concentrações de cloreto no suor. Objetivos: pesquisar a correlação entre os níveis de cloreto no teste do suor e a idade ao diagnóstico de indivíduos com fibrose cística e comparar as concentrações iônicas do cloreto entre os sexos, diferentes faixas etárias e três grupos diversos de genótipos do CFTR. Metodologia: realizou-se um estudo de corte transversal, incluindo sujeitos de 0 a 20 anos, com diagnóstico confirmado de fibrose cística. Os indivíduos selecionados foram agrupados de acordo com as variáveis analisadas. Calcularam-se os valores descritivos das concentrações de íons cloreto de cada grupo. Utilizou-se o teste de Spearman para a análise da correlação entre a idade ao diagnóstico e os níveis de cloreto no suor. Resultados: 64 indivíduos foram incluídos no estudo, sendo 51,56% do sexo masculino. A mediana (Min ­ Max) da idade ao diagnóstico foi de 7 meses (1-206). Não foi observa da correlação entre a idade dos indivíduos ao diagnóstico e os níveis de cloreto no suor. As concentrações medianas de cloreto foram maiores nos escolares (106 mEq/l), no sexo feminino (102 mEq/l) e nos heterozigotos F508del/Classe I a III (108 mEq/l); e menores nos adolescentes (100 mEq/l) e nos heterozigotos F508del/Classes IV a VI (77 mEq/l). Conclusão: os níveis de cloreto no suor não apresentaram correlação com a idade dos indivíduos ao diagnóstico. A variação considerável dos níveis iônicos entre os grupos de diferentes genótipos corrobora que o teste do suor é um bom preditor da avaliação funcional do canal CFTR.

Introduction: cystic fibrosis is the most common autosomal recessive disorder in Caucasian populations and its etiology is associated with pathogenic variants in the CFTR gene. The sweat test is considered the gold standard for the diagnosis of the disease. Some studies suggest that CFTR genotype and age affect sweat chloride concentrations. Objectives: to investigate the correlation between sweat chloride levels and age at diagnosis of individuals with cystic fibrosis and to compare ionic chloride concentrations among sexes, different age groups and three distinct groups of CFTR genotypes. Methodology: a cross-sectional study was conducted, which included CF subjects from 0 to 20 years of age. The selected individuals were clustered on the variables in analysis. The description values for chloride ion concentrations in each group were calculated. The Spearman's test was used to analyze the correlation between the age at diagnosis and sweat chloride levels. Results: 64 individuals were included, 51,56% male. The median (Min ­ Max) age at diagnosis was 7 months (1-206). There was no correlation between the age at diagnosis and sweat chloride levels. The median of the chloride concentrations were higher for schoolchildren (106 mEq/l), females (102 mEq/l) and heterozygous F508del/Classes I to III (108 mEq/l), and reached the lowest values for teenagers (100 mEq/l) and heterozygous F508del/Classes IV to VI (77 mEq/l). Conclusion: sweat chloride levels did not correlate with the age of individuals at diagnosis. The substantial variation of ionic levels among groups of distinct genotypes corroborates that the sweat test is a good predictor for functional assessment of the CFTR channel.

Lung transplantation for cystic fibrosis: a case report and literature review / 器官移植

Objective To investigate the clinical efficacy and prognosis of lung transplantation in the treatment of cystic fibrosis (CF). Methods Clinical data of one patient with end-stage CF undergoing allogeneic bilateral lung transplantation were retrospectively analyzed. Clinical characteristics, diagnostic methods and treatment strategies of the CF recipient were summarized. Results The recipient had suffered from relevant symptoms since childhood including repeated cough and purulent sputum for 30 years, complicated with recurrent pulmonary infection combined with acute exacerbation, chronic sinusitis and extremely severe malnutrition. Prior to lung transplantation, the patient had to depend upon the invasive ventilator due to respiratory muscle weakness, and admitted to intensive care unit (ICU) for a long time. Imaging examination revealed multiple cystic columnar bronchiectasis accompanied with infection in bilateral lungs. The diagnosis of CF was further confirmed by sweat test and gene detection. The recipient underwent bilateral lung transplantation on August 17, 2017 and received rehabilitation treatment. The lung function was gradually restored to normal. The recipient had obtained the same quality of life to the healthy counterparts since the date of manuscript submission (over 2 years). Conclusions Lung transplantation is an efficacious treatment for end-stage CF, which can not only save patients' lives, but also significantly improve the quality of life of patients.

Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis / Dosagem da concentração dos íons cloreto e sódio na saliva e no suor para o reconhecimento de pacientes com fibrose cística

Abstract Objective: Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥ 60 mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration and sweat chloride concentration, and between saliva sodium concentration and sweat sodium concentration, in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis. Methods: There were 160 subjects enrolled: 57/160 (35.70%) patients with cystic fibrosis and two known CFTR mutations and 103/160 (64.40%) healthy controls subjects. Saliva ion concentration was analyzed by ABL 835 Radiometer® equipment and, sweat chloride concentration and sweat sodium concentration, respectively, by manual titration using the mercurimetric procedure of Schales & Schales and flame photometry. Statistical analysis was performed by the chi-squared test, the Mann -Whitney test, and Spearman's correlation. Alpha = 0.05. Results: Patients with cystic fibrosis showed higher values of sweat chloride concentration, sweat sodium concentration, saliva chloride concentration, and saliva sodium concentration than healthy controls subjects (p-value < 0.001). The correlation between saliva chloride concentration and sweat chloride concentration showed a positive Spearman's Rho (correlation coefficient) = 0.475 (95% CI = 0.346 to 0.587). Also, the correlation between saliva sodium concentration and sweat sodium concentration showed a positive Spearman's Rho = 0.306 (95% CI = 0.158 to 0.440). Conclusions: Saliva chloride concentration and saliva sodium concentration are candidates to be used in cystic fibrosis diagnosis, mainly in cases where it is difficult to achieve the correct sweat amount, and/or CFTR mutation screening is difficult, and/or reference methods for sweat test are unavailable to implement or are not easily accessible by the general population.

Resumo Objetivo: O diagnóstico da fibrose cística depende do valor da concentração de íons de cloreto no teste do suor (≥ 60 mEq/mL - reconhecido como o indicador-padrão para o diagnóstico da doença). Além disso, as glândulas salivares expressam a proteína RTFC igualmente às glândulas sudoríparas. Nesse contexto, nosso objetivo foi verificar a correlação da concentração de cloreto na saliva e a concentração de cloreto no suor e entre a concentração de sódio na saliva e a concentração de sódio no suor em pacientes com fibrose cística e indivíduos controles saudáveis, como uma ferramenta para diagnóstico de fibrose cística. Métodos: Contamos com a participação de 160 indivíduos [57/160 (35,70%) com fibrose cística e duas mutações no gene RTFC conhecidas e 103/160 (64,40%) indivíduos controles saudáveis]. A concentração de íons na saliva foi analisada pelo equipamento ABL 835 da Radiometer® e a concentração de cloreto no suor e sódio no suor, respectivamente, por titulação manual utilizando o método mercurimétrico de Schales & Schales e fotometria de chama. A análise estatística foi realizada pelo teste qui-quadrado, pelo teste de Mann-Whitney e pela correlação de Spearman. Alpha = 0,05. Resultados: Os pacientes com fibrose cística apresentaram maiores valores na concentração de cloreto no suor, concentração de sódio no suor, concentração de cloreto na saliva e concentração de sódio na saliva do que os indivíduos-controle saudáveis (valor de p < 0,001). A correlação entre as concentrações de cloreto na saliva e cloreto no suor mostrou Rho de Spearman (coeficiente de correlação) positivo = 0,475 (IC de 95% = 0,346 a 0,587). Além disso, a correlação entre concentração de sódio na saliva e concentração de sódio no suor mostrou Rho de Spearman positivo = 0,306 (IC de 95% = 0,158 a 0,440). Conclusões: A concentração de cloreto na saliva e a concentração de sódio na saliva são candidatas a ser usadas como diagnóstico de fibrose cística, principalmente em casos em que é difícil atingir a quantidade correta de suor, e/ou o exame da mutação RTFC é difícil e/ou o método de referência para o teste do suor não se encontra disponível ou não é de fácil acesso ao público em geral.

Aquagenic Wrinkling of Skin: A Screening Test for Cystic Fibrosis

Objectives: To study the utility of aquagenic wrinkling asscreening test for children with cystic fibrosis.Design: Evaluation of diagnostic test.Setting: Pediatric Chest Clinic, and Pediatric Wards of a tertiarycare hospital in New Delhi.Participants: Three groups (children with cystic fibrosis,carriers of cystic fibrosis, and controls).Method: Time taken to develop aquagenic wrinkling wasmeasured. The test was performed by asking the enrolled subjectto put their one hand in water and was checked for development ofwrinkling every minute, and a photograph was also taken everyminute.Results: A total of 64 children with cystic fibrosis, 64 controls and64 carriers were enrolled in the study. Median (IQR) time todevelop aquagenic wrinkling in the three groups was 2 (1.5,3)minutes, 4 (3,5) minutes and 8 (5,11) minutes, respectively. Theoptimal cut-off was calculated as 3 minutes by Receiveroperating characteristic curve with a sensitivity and specificityfor identification of children with cystic fibrosis as 81% and 57%,respectively. The area under curve was 76.5%. The 3 minutecut-off for development of aquagenic wrinkling was applied to 54children referred for sweat test. 20 children had sweat chloridevalues of ≥60 mEq/l and diagnosed as cystic fibrosis. 15 of thesedeveloped aquagenic wrinkling at ≤3 minutes, giving a sensitivityof 75%.Conclusion: In places with no facility for sweat test, childrenwith phenotype compatible with cystic fibrosis who developaquagenic wrinkling in 3 minutes may be diagnosed as probablecystic fibrosis and referred for confirmation by sweat tes

Research progress in diagnosis and treatment of cystic fibrosis / 中华实用儿科临床杂志

Cystic fibrosis(CF)is a multisystem disorder caused by mutation in the gene for cystic fibrosis transmembrane conductance regulator.Early diagnosis and early treatment are the key to prevent and control CF.With the development of molecular genetics, the detection rate of CF is greatly improved, even during the neonatal period, CF can be diagnosed.The newly developed drugs and comprehensive therapies have greatly prolonged the survival time of the patients.With the new understanding of the disease, the early diagnosis and treatment of CF are possible.Now, the diagnostic methods and treatment progress of CF are reviewed.

Test del sudor en rango intermedio: desafío diagnóstico / Intermediate sweat chloride values: a diagnostic challenge

There is a group of patients with sweat test values at intermediate range (30-59 mmol / l chloride) whose diagnosis is difficult to be classified, especially after the introduction of neonatal screening for cystic fibrosis in some countries. This has introduced new terminology and panels of experts from the United States and Europe have created guidelines for the evaluation and management of these individuals. There are few studies on the evolution of these patients, however all of them agree on a more benign evolution than for those who have altered sweat test (sweat chloride higher to 60 mmol /l). The clinical monitoring is essential to obtain a proper diagnosis.

Existe un grupo de pacientes con valores de test de sudor en rango intermedio (30-59 mmol/l de cloro) cuyo diagnóstico es difícil de catalogar, especialmente luego de la introducción en algunos países del tamizaje neonatal para fibrosis quística. Se ha introducido nueva terminología y paneles de expertos de Estados Unidos y Europa han creado guías para la evaluación y manejo de estos individuos. Existen escasas descripciones sobre la evolución de estos pacientes aunque coinciden en una evolución más benigna que en aquellos que tienen test de sudor alterado (cloro mayor a 60 mmol/l).El seguimiento clínico es fundamental para llegar a un diagnóstico adecuado.

Test del sudor, técnica y errores / Sweat test, technique and errors

The quantitative measurement of the sweat electrolytes continue being the gold standard for cystic fibrosis diagnosis. Is very important that centers dedicated to diagnosis and treatment of the disease, have trained personnel in order to measure chloride sweat with the accepted technique in international literature. This paper reviews the main aspects and steps of the quantitative measurement of the sweat chloride concentration, obtained with pilocarpine iontophoresis and the common mistakes commited when realizing it.

La medición cuantitativa de los electrolitos en sudor continúa siendo el examen diagnóstico de la fibrosis quística. Por ello es fundamental que los centros dedicados al diagnóstico y tratamiento de esta enfermedad, cuenten con laboratorios con personal entrenado y capacitado para medir el cloro en el sudor con la técnica aceptada en la literatura. Este artículo revisa los principales aspectos y etapas de la medición cuantitativa de la concentración de cloro en el sudor obtenido con iontoforesis de pilocarpina y los errores más comunes que se cometen al realizarlo.

Condutividade e teste quantitativo coulométrico na triagem neonatal para fibrose cística / Sweat conductivity and coulometric quantitative test in neonatal cystic fibrosis screening

Resumo Objetivo Comparar os resultados obtidos no teste do suor pelo método da condutividade e a dosagem coulométrica de cloreto no suor em recém0nascidos (RN) suspeitos da triagem neonatal para fibrose cística (FC). Métodos O teste do suor foi feito simultaneamente pelos dois métodos em crianças com e sem FC. Os valores de corte para confirmar FC foram na condutividade > 50 mmol/L e no teste coulométrico > 60 mmol/L. Resultados Fizeram o teste do suor por condutividade e dosagem coulométrica simultaneamente 444 RN sem FC (185 do sexo masculino, 234 do feminino e 24 não informado) e obtiveram resultado mediano de 32 mmol/L e 12 mmol/L respectivamente. Para os noventa RN com FC os valores medianos de condutividade e dosagem coulométrica foram 108 mmol/L e 97 mmol/L respectivamente. O índice de falso positivo para condutividade foi de 16,7% e em todos os pacientes FC foi superior a 50 mmol/L, o que confere ao método 100% de sensibilidade (IC 95% = 93,8 a 97,8), especificidade de 96,2% (IC 95% = 93,8 a 97,8), valor preditivo positivo 83,3 (IC 95% = 74,4 a 91,1), valor preditivo negativo 100% (IC 95% = 90,5 a 109,4) e acurácia 9,8%. A correlação entre os métodos foi de r = 0,97 (p > 0,001).O melhor valor de corte sugerido foi de 69,0 mmol/L, coeficiente de kappa = 0,89. Conclusão O teste da condutividade apresentou excelente correlação com o quantitativo coulométrico, alta sensibilidade e especificidade e pode ser usado no diagnóstico da FC em crianças detectadas pela triagem neonatal.

Abstract Objective To compare the results obtained with the sweat test using the conductivity method and coulometric measurement of sweat chloride in newborns (NBs) with suspected cystic fibrosis (CF) in the neonatal screening program. Methods The sweat test was performed simultaneously by both methods in children with and without CF. The cutoff values to confirm CF were >50 mmol/L in the conductivity and >60 mmol/L in the coulometric test. Results There were 444 infants without CF (185 males, 234 females, and 24 unreported) submitted to the sweat test through conductivity and coulometric measurement simultaneously, obtaining median results of 32 mmol/L and 12 mmol/L, respectively. For 90 infants with CF, the median values of conductivity and coulometric measurement were 108 mmol/L and 97 mmol/L, respectively. The false positive rate for conductivity was 16.7%, and was higher than 50 mmol/L in all patients with CF, which gives this method a sensitivity of 100% (95% CI: 93.8-97.8), specificity of 96.2% (95% CI: 93.8-97.8), positive predictive value of 83.3% (95% CI: 74.4-91.1), negative predictive value of 100% (95% CI: 90.5-109.4), and 9.8% accuracy. The correlation between the methods was r = 0.97 (p > 0.001). The best suggested cutoff value was 69.0 mmol/L, with a kappa coefficient = 0.89. Conclusion The conductivity test showed excellent correlation with the quantitative coulometric test, high sensitivity and specificity, and can be used in the diagnosis of CF in children detected through newborn screening.

Comparação entre o método clássico de Gibson e Cooke e o teste da condutividade no suor em pacientes com e sem fibrose cística / Comparison between classic Gibson and Cooke technique and sweat conductivity test in patients with and without cystic fibrosis

OBJETIVO: Comparar os valores de cloro no suor obtidos pelo teste quantitativo da iontoforese pela pilocarpina (teste clássico) com os valores de condutividade no suor obtidos pelo sistema de coleta por Macroduct® em pacientes com e sem fibrose cística (FC). O custo e tempo despendidos na execução de cada teste foram também analisados. MÉTODOS: O teste do suor pelas duas técnicas foi realizado simultaneamente, em pacientes com e sem FC. Os pontos de corte para a condutividade para excluir ou diagnosticar FC foram < 75 e > 90 mmol/L, respectivamente, e, para o teste clássico, cloro < 60 e > 60 mmol/L. RESULTADOS: Cinquenta e dois pacientes com FC (29 do sexo masculino e 23 do sexo feminino; de 1,5 a 18,2 anos) realizaram o teste do suor pelas duas técnicas, apresentando valores medianos de cloro e condutividade no suor de 114 e 122 mmol/L, respectivamente. Em todos eles, a condutividade foi > 95 mmol/L, o que conferiu ao teste 100 por cento de sensibilidade (IC95 por cento 93,1-100). Cinquenta pacientes sem FC (24 do sexo masculino e 26 do sexo feminino; de 0,5 a 12,5 anos) apresentaram valores medianos de cloro e condutividade no suor de 15,5 e 30 mmol/L, respectivamente. Em todos os casos, a condutividade foi < 70 mmol/L, o que conferiu ao teste 100 por cento de especificidade (IC95 por cento 92,9-100). O tempo despendido na execução dos testes foi significativamente menor com o teste da condutividade, e o seu custo também foi inferior. CONCLUSÕES: O teste da condutividade apresentou alta sensibilidade e especificidade, e houve boa correspondência entre os testes. O tempo de execução foi mais rápido e o custo inferior na aplicação do teste da condutividade em relação ao teste clássico.

OBJECTIVE: To compare sweat chloride values obtained by quantitative pilocarpine iontophoresis (classic test) with the sweat conductivity values obtained using Macroduct® collection system in patients with and without cystic fibrosis (CF). The cost and time spent to carry out each test were also analyzed. METHODS: The sweat test using both techniques was performed at the same time in patients with and without CF. Conductivity cutoff values to rule out or diagnose CF were < 75 and > 90 mmol/L, respectively, and for the classic test the chloride values were < 60 and > 60 mmol/L. RESULTS: Fifty-two patients with CF (29 males and 23 females; aged from 1.5 to 18.2 years) underwent the sweat test using both techniques, showing median sweat chloride and conductivity values of 114 and 122 mmol/L, respectively. In all of them, conductivity was > 95 mmol/L, which provided the test with 100 percent sensitivity (95 percentCI 93.1-100). Fifty patients without CF (24 males and 26 females; aged from 0.5 to 12.5 years) had median sweat chloride and conductivity values of 15.5 and 30 mmol/L, respectively. In all cases, conductivity was < 70 mmol/L, which provided the test with 100 percent specificity (95 percentCI 92.9-100). Time spent to perform the tests was significantly shorter for the conductivity test, and its cost was also lower. CONCLUSIONS: The conductivity test showed high sensitivity and specificity, and there was good correspondence between the tests. The time spent to carry out the conductivity test was shorter and the cost was lower in comparison with the classic test.

Fibrosis quística: aspectos diagnósticos / Cystic fibrosis: diagnosis

La fibrosis quística (FQ) es una de las enfermedades genéticas mortales más frecuentes en la raza caucásica. Se caracteriza por una disfunción de las glándulas exocrinas, con insuficiencia pancreática y bronconeumopatía crónica. Es una enfermedad de transmisión autonómica recesiva, se sabe que el gen defectuoso está localizado en el cromosoma 7 humano, conocido como gen regulador de la conductancia transmembrana de la fibrosis quística (CFTR),y que de las más de mil mutaciones de este gen, la mutación DF508 es la más común, pues se halla en aproximadamente 70% de los alelos CFTR defectuosos. El diagnóstico de la FQ se ha basado clásicamente en la determinación de por lo menos 2-3 determinaciones positivas de electrólitos en sudor, junto con uno de los siguientes criterios clínicos: íleo meconial, historia familiar de FQ, insuficiencia pancreática exocrina, enfermedad pulmonar crónica, azoospermia obstructiva y síndrome de pérdida de sal. Los criterios diagnósticos actuales incluyen, junto a la presencia de las características clínicas, dos determinaciones de concentraciones de cloro en sudor superior a 60 mmol/l, o demostración de alteraciones en el transporte iónico a través del epitelio nasal (diferencia de potencial nasal) o la detección de dos mutaciones reconocidas de FQ.

Cystic fibrosis (CF) is one of the most frequent inherited mortal diseases in Caucasian population. Dysfunction in exocrine glands is described in CF patients, with severe pancreatic insufficiency and chronic lung disease. CF is inherited as an autosomal recessive disorder. More than 1000 disease-associated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been described. DF508 mutation is the most common mutation in the CF gen. Diagnosis in CF is based on clinical and laboratory tests findings. Meconial ileus, CF in other relatives, chronic lung disease, congenital absence of the vas deferens with azoospermia are among other clinical findings, main criteria in CF patients. Two positive results in sweat chloride test , or demonstration in nasal epithelial ionic transport alteration (nasal potential difference) and identification of two CF mutations in the patient are laboratory findings in CF.

Determinación de las mutaciones más frecuentes en pacientes con fibrosis quística, Ecuador. Análisis de mutaciones en el gen CFTR por técnica de hibridación reversa in situ y heterodúplex: junio 1996–enero 2004 / The most frequent mutation in patients with Cystic Fybrosis in Ecuador. Using the techniques of reverse in situ hybridization and heteroduplex to analyze mutations of the CFTR gene: june 1996–january 2004

La fibrosis quística (FQ) es la enfermedad hereditaria más común y letal que existe; es de carácter autosómico recesivo, de afección multisistémica, causada por una mutación en el gen CFTR (cystic fibrosis transmembrane regulator) ubicado en el brazo largo del cromosoma 7 (7q31.2). Tipo de estudio: descriptivo. Justificativo: Ecuador es uno de los pocos países latinoamericanos en los que aún no se conoce la verdadera incidencia y frecuencia de las mutaciones que afectan a los pacientes que padecen de fibrosis quística. Objetivos: Establecer el primer registro molecular de las mutaciones más frecuentes de la población de FQ ecuatoriana. Establecer la incidencia estimada de la enfermedad en el Ecuador. Resultados: Se incluyeron 62 pacientes en el estudio desde 1996 al 2004. Se determinó una incidencia estimada de 1:11.252 nacidos vivos durante el año 2004, con un estimado de 25 nacidos vivos afectos de fibrosis quística durante el referido año. La frecuencia de las mutaciones halladas fue ∆F508 37.1%, G85E 8.9%, G542X 2.4%, N1303K 2.4%, G551D 1.6% y R334W 0.8%. La frecuencia de la mutación G85E (8,9%) encontrada en Ecuador es la más alta a nivel mundial, incluso mayor a la del sur de Grecia de donde se cree que es originaria dicha mutación. Conclusiones y recomendaciones: La sensibilidad de los métodos utilizados (heterodúplex e hibridación reversa in situ) en relación a la población ecuatoriana fue 53,22%, que representa el porcentaje de mutaciones que se pudieron encontrar. Aunque aceptable en relación a los resultados encontrados a nivel mundial, este porcentaje plantea la imprescindible necesidad de utilizar secuenciación para establecer ese gran porcentaje de mutaciones que permanecen como no conocidas (WT).

Cystic Fybrosis is a autosomal recessive disease that is very common. It affects multi-organs and caused by the mutation of CFTR gene ( cystic fibrosis transmembrane regulator) which is found on the long arm of chromosome 7. Type of study: descriptive. Justification: Ecuador is one of the countries in Latin America that we still don’t know the incidence and frequency of the mutations that affect patients with Cystic Fybrosis. Objectives: To establish which are the most common mutations in patients with Cystic Fybrosis in Ecuador. To establish the incidence of this disease in Ecuador. Results: In this study 62 patients were found during 1996 to 2004. An incidence of 1:11252 born alive a total of 25 newborns had cystic fybrosis during this year. The frequencies for the mutations found were: ∆F508:37.1%, G85E: 8.9%, G542X: 2.4%, N1303: 2.4%, G551D: 1.6%, R334W: 0.8%. The frequency of gene mutation G85E has been found to be the highest in Ecuador other to other countries including South of Greece where the mutation originated. Conclusion and Recommendations: The sensitivity of the techniques used was 53.22% which represents the percentage of mutations that were found. Even though this is acceptable in relation to the results found worldwide, this percentage shows us how important it is to use mutation screening to establish the percentage of mutations that are unknown.

Prolonged survival following meconium ileus

A rare case is presented of a boy who is still alive 17 years after surgery for meconium ileus. Soon after the surgery the patient developed manifestations of pulmonary imvolvement and later, of pancreatic insufficiency. Diagnosis was made by means of the sweat testThe patients prolonged survival is attributed to adequate therapy of his relatively quiescent pulmonary lesion. With the good therapeutic program now available for the pulmonary lesion. With the good therapeutic program now available for the pulmonary complications, we should expect that a good number of the 50% who now survive surgery for meconium ileus will have the same chance at longer life span.(Summary)

Cystic fibrosis: a case presented with recurrent bronchiolitis in infancy in a Korean male infant

The aim of this case report is to draw the attention to the occurrence of cystic fibrosis (C.F.) in a Korean infant and thus increase the awareness for the diagnosis. The male infant was presented with a history of recurrent bronchiolitis manifested by severe cough, wheeze and dyspnea from three weeks of age, in whom the diagnosis of C.F. was clinically suspected and was confirmed by demonstration of two elevated sweat chloride levels (97 mEq/L and 99 mEq/L) in the patient. The diagnosis was delayed because the main manifestations of C.F. were the same as the main symptoms of common diseases such as cough, diarrhea and failure to thrive. C.F. is probably underdiagnosed in Korean population both because the diagnosis is not considered since the disease is thought to be uncommon or even not to occur and because diagnostic facilities including the quantitative iontophoresis sweat test are lacking.