RESUMEN
INTRODUCTION: Chronic granulomatous disease (CGD) is characterized by an alteration of the neutrophil oxidative function. Its inheritance patterns are linked to the X chromosome (X-linked CGD) and autosomal recessive (AR CGD). The dihydrorhodamine (DHR) assay is used for the diagnosis and detection of carriers and provides information on inheritance patterns. OBJECTIVE: To detect CGD cases in chil dren with recurrent infections and to evaluate their female relatives through the DHR assay to iden tify carriers and obtain information about possible inheritance patterns. PATIENTS AND METHOD: 107 patients (<18 years of age) with clinical suspicion of CGD such as pneumonia, lymphadenopathies, and abscesses were included, referred by physicians from public hospitals between 2014 and 2017. Six female relatives of children with CGD were also included. The DHR assay was performed on all patient samples and the results were expressed as neutrophils stimulation index (SI). RESULTS: The median age of patients was 3 years and 62/107 of them were male. The average SI was 39.7±13.8 and a complete shift of DHR was found in 101/107 children. In 2/107 children, no DHR shift was observed (SI=1.0) indicating possible X-linked CGD, and a third child showed a slight DHR shift (SI=4.8) compatible with AR CGD. 5/6 female relatives presented a bimodal pattern, showing a carrier status. CONCLUSIONS: Three cases of CGD and five female carriers were detected through the DHR assay, being the first time that this technique was used in Paraguay. Information on the most likely inheri tance patterns, two X-linked CGD, and one AR CGD case was also obtained.
Asunto(s)
Enfermedad Granulomatosa Crónica/diagnóstico , Rodaminas/sangre , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Femenino , Citometría de Flujo , Enfermedad Granulomatosa Crónica/sangre , Enfermedad Granulomatosa Crónica/genética , Humanos , Lactante , Patrón de Herencia , MasculinoRESUMEN
Resumen: Introducción: La enfermedad granulomatosa crónica (EGC) se caracteriza por una alteración de la función oxidativa de neutrófilos, presentando herencia ligada al cromosoma X (EGC LX) y autosómica recesiva (EGC AR). El ensayo de dihidrorodamina (DHR) es utilizado para el diagnóstico y detección de portadoras, además proporciona información sobre patrones de herencia. Objetivo: Detectar casos de EGC en niños con infecciones recurrentes y evaluar a sus familiares femeninos mediante el ensayo de DHR, para identificar portadoras y obtener información acerca de posibles patrones de herencia. Pacientes y Método: Fueron incluidos 107 pacientes (<18 años de edad) con sospecha clínica de EGC como neumonías, linfadenopatías y abscesos, remitidos por médicos de hospitales públicos, del 2014 al 2017. Además, se incluyeron seis mujeres, familiares de los niños con EGC. A las muestras de los pacientes se aplicó el ensayo DHR, expresando los resultados como índice de estimulación de neutrófilos (IE). Resultados: La mediana de edad de los pacientes fue de 3 años y 62/107 fueron varones. El IE promedio fue 39,7 ± 13,8 y 101/107 niños exhibieron un cambio completo de fluorescencia de DHR. En 2/107 niños no se observó dicho cambio (IE = 1,0), lo cual indica posible EGC LX, y un tercer niño mostró un leve cambio (IE = 4,8), compatible con EGC AR. En 5/6 mujeres se encontró un patrón bimodal, indicando un estado de portadora. Conclusiones: Fueron detectados tres casos de EGC y cinco portadoras mediante el ensayo de DHR, realizado por primera vez en Paraguay. También se obtuvo información sobre los posibles patrones de herencia, EGC LX en dos familias y un caso probable de EGC AR.
Abstract: Introduction: Chronic granulomatous disease (CGD) is characterized by an alteration of the neutrophil oxidative function. Its inheritance patterns are linked to the X chromosome (X-linked CGD) and autosomal recessive (AR CGD). The dihydrorhodamine (DHR) assay is used for the diagnosis and detection of carriers and provides information on inheritance patterns. Objective: To detect CGD cases in chil dren with recurrent infections and to evaluate their female relatives through the DHR assay to iden tify carriers and obtain information about possible inheritance patterns. Patients and Method: 107 patients (<18 years of age) with clinical suspicion of CGD such as pneumonia, lymphadenopathies, and abscesses were included, referred by physicians from public hospitals between 2014 and 2017. Six female relatives of children with CGD were also included. The DHR assay was performed on all patient samples and the results were expressed as neutrophils stimulation index (SI). Results: The median age of patients was 3 years and 62/107 of them were male. The average SI was 39.7±13.8 and a complete shift of DHR was found in 101/107 children. In 2/107 children, no DHR shift was observed (SI=1.0) indicating possible X-linked CGD, and a third child showed a slight DHR shift (SI=4.8) compatible with AR CGD. 5/6 female relatives presented a bimodal pattern, showing a carrier status. Conclusions: Three cases of CGD and five female carriers were detected through the DHR assay, being the first time that this technique was used in Paraguay. Information on the most likely inheri tance patterns, two X-linked CGD, and one AR CGD case was also obtained.