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BACKGROUND: Rare diseases are pathologies that affect less than 1 in 2000 people. They are difficult to diagnose due to their low frequency and their often highly heterogeneous symptoms. Rare diseases have in general a high impact on the quality of life and life expectancy of patients, which are in general children or young people. The advent of high-throughput sequencing techniques has improved diagnosis in several different areas, from pediatrics, achieving a diagnostic rate of 41% with whole genome sequencing (WGS) and 36% with whole exome sequencing, to neurology, achieving a diagnostic rate between 47 and 48.5% with WGS. This evidence has encouraged our group to pursue a molecular diagnosis using WGS for this and several other patients with rare diseases. RESULTS: We used whole genome sequencing to achieve a molecular diagnosis of a 7-year-old girl with a severe panvascular artery disease that remained for several years undiagnosed. We found a frameshift variant in one copy and a large deletion involving two exons in the other copy of a gene called YY1AP1. This gene is related to Grange syndrome, a recessive rare disease, whose symptoms include stenosis or occlusion of multiple arteries, congenital heart defects, brachydactyly, syndactyly, bone fragility, and learning disabilities. Bioinformatic analyses propose these mutations as the most likely cause of the disease, according to its frequency, in silico predictors, conservation analyses, and effect on the protein product. Additionally, we confirmed one mutation in each parent, supporting a compound heterozygous status in the child. CONCLUSIONS: In general, we think that this finding can contribute to the use of whole genome sequencing as a diagnosis tool of rare diseases, and in particular, it can enhance the set of known mutations associated with different diseases.
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Arteriopatías Oclusivas/genética , Proteínas de Ciclo Celular/genética , Cardiopatías Congénitas/genética , Enfermedades Raras/genética , Factores de Transcripción/genética , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/patología , Arterias/diagnóstico por imagen , Arterias/patología , Niño , Femenino , Mutación del Sistema de Lectura/genética , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/patología , Homocigoto , Humanos , Linaje , Enfermedades Raras/diagnóstico , Enfermedades Raras/patología , Secuenciación Completa del GenomaRESUMEN
The incidence of nephrolithiasis continues to rise. Previously, we showed that a monogenic cause could be detected in 11.4% of individuals with adult-onset nephrolithiasis or nephrocalcinosis and in 16.7-20.8% of individuals with onset before 18 years of age, using gene panel sequencing of 30 genes known to cause nephrolithiasis/nephrocalcinosis. To overcome the limitations of panel sequencing, we utilized whole exome sequencing in 51 families, who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis to identify the underlying molecular genetic cause of disease. In 15 of 51 families, we detected a monogenic causative mutation by whole exome sequencing. A mutation in seven recessive genes (AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1), in one dominant gene (SLC9A3R1), and in one gene (SLC34A1) with both recessive and dominant inheritance was detected. Seven of the 19 different mutations were not previously described as disease-causing. In one family, a causative mutation in one of 117 genes that may represent phenocopies of nephrolithiasis-causing genes was detected. In nine of 15 families, the genetic diagnosis may have specific implications for stone management and prevention. Several factors that correlated with the higher detection rate in our cohort were younger age at onset of nephrolithiasis/nephrocalcinosis, presence of multiple affected members in a family, and presence of consanguinity. Thus, we established whole exome sequencing as an efficient approach toward a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years.
Asunto(s)
Secuenciación del Exoma , Mutación , Nefrocalcinosis/genética , Nefrolitiasis/genética , Adolescente , Edad de Inicio , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Herencia , Humanos , Lactante , Masculino , Nefrocalcinosis/diagnóstico por imagen , Nefrocalcinosis/epidemiología , Nefrolitiasis/diagnóstico por imagen , Nefrolitiasis/epidemiología , Linaje , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Tomografía Computarizada por Rayos X , Ultrasonografía , Adulto JovenRESUMEN
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Summary: Introduction: the idiopathic nephrotic syndrome (INS) is the most common glomerulopathy in pediatrics. The purpose of this study is to estimate the INS incidence in pediatric public health patients and to describe their response to treatment and their evolutionary characteristics and complications. Methods: a descriptive study was carried out of a historical cohort of patients under 15 years of age with first time INS assisted in the Nephrological Clinic of the Pereira Rossell Hospital Center between 01/01/2009 - 12/31/2013, monitored until 12/31/ 2015, users of the State Health Services (ASSE). Their annual incidence was estimated according to data obtained from the National Data System Report (SINADI) of the Ministry of Public Health. We recorded age, sex, height, body mass index, response to initial treatment and evolution and followed them up >12 months. Results: we included 42 patients with a male / female ratio 2.2 / 1; the SNI annual incidence in the ASSE population was 3.05 / 100,000 children under 15 years of age. 34 were cortico-sensitive (CS) and 8 cortico-resistant (CR). The mean age of the first incident was 5 years in CS and 2 years 10 months in CR. The evolution was analyzed in the 33 patients monitored for a period of time >12 months, with a mean follow-up of 4 years ± 1 year 9 months; In these children, the frequency of CS was 78.7% (n = 26) and of RC 21.3% (n = 7). Within the CS, there were 10 (38.6%) cortico-dependents / frequent relapsers (DC), 8 had sporadic relapses and 8 did not relapse. Among the DCs, 5 received cyclophosphamide, in one patient prednisone was suspended at 3 months, in 2 of them the dose was lowered and the other 2 did not respond, one of them achieved sustained remission with cyclosporine. Of the 7 RCs, 4 had initial remission with cyclosporine, 1 partial remission and 2 were resistant; 3 received mycophenolate mofetil, 2 did not respond, and 1 had partial remission. The biopsy in all the RCs showed focal and segmental hyalinosis. The genetic study for NPHS2 and WT1 carried out on 4 patients was negative. At the end of follow-up, all CS patients were in remission, 16/26 without treatment. Among the RCs, 2 were in remission with cyclosporine, 4 maintained nephrotic proteinuria (one of them with a drop in glomerular filtration rate of 60 ml/min/1.73m2 sc), and another was on chronic dialysis. Serious infectious complications occurred in 5 CR and 2 CS patients. One CD and one CR patient developed chronic arterial hypertension. In CD and RC, a significant difference was observed in the Z score of the BMI and height between the beginning and the end of the follow-up. Conclusions: the calculated incidence includes only patients treated by the State Health Services in our country; it does not reflect the global incidence at national level, and it is comparable to that of other series. The evolution of CS and CR patients was also similar to those described. The growth of children exposed to long-term corticosteroid treatment was affected. For best results, these patients should be offered customized treatment according to current recommendations.
Resumo: Introdução: a síndrome nefrótica idiopática (SNI) é a glomerulopatia mais comum em pediatria. O objetivo do estudo é estimar a incidência em pacientes usuários da assistência pública e descrever a resposta ao tratamento, as características evolutivas e as complicações. Métodos: realizou-se um estudo descritivo de uma coorte histórica de pacientes menores de 15 anos de idade atendidos na Policlínica Nefrológica do Centro Hospitalar Pereira Rossell com SNI entre 01/01/2009 - 31/12/2013, controlados até 31/12 / 2015, usuários dos Serviços de Saúde do Estado (ASSE). Estimou-se a incidência anual em pacientes de ASSE menores de 15 anos de idade, segundo dados do relatório do Sistema Nacional de Dados (SINADI) do Ministério da Saúde Pública. Se registraram a idade, sexo, altura, índice de massa corporal, resposta ao tratamento inicial e evolução dos pacientes com seguimento >12 meses. Resultado: foram incluídos 42 pacientes com relação sexo masculino/feminino 2,2/1; a incidência anual de SNI na população ASSE foi de 3,05/100.000 crianças menores de 15 anos de idade. 34 eram córtico-sensíveis (CS) e 8 córtico-resistentes (CR). A idade média do começo da doença foi de 5 anos no CS e 2 anos e 10 meses no CR. A evolução foi analisada nos 33 pacientes controlados por um período de tempo >12 meses, com seguimento médio de 4 anos ± 1 ano 9 meses; nessas crianças, a frequência de SC foi de 78,7% (n = 26) e de RC de 21,3% (n = 7). No CS, havia 10 (38,6%) corticodependentes/recidivas frequentes (CD), 8 tiveram recidivas esporádicas e 8 não tiveram recidiva. Dentre as CDs, 5 receberam ciclofosfamida, numa criança a prednisona foi suspensa aos 3 meses, em 2 delas a dose foi diminuída e as outras 2 não responderam, uma delas obteve remissão sustentada com ciclosporina. Dos 7 casos de CRs, 4 tiveram remissão inicial com ciclosporina, 1 remissão parcial e 2 foram resistentes; 3 receberam micofenolato de mofetil, 2 não responderam e 1 teve remissão parcial. A biópsia em todos os CRs mostrou hialinose focal e segmentar. O estudo genético para NPHS2 e WT1 realizado em 4 pacientes foi negativo. Ao final do acompanhamento, todos os pacientes com SC estavam em remissão, 16/26 sem tratamento. Entre os CRs, 2 estavam em remissão com ciclosporina, 4 mantinham a proteinúria nefrótica (um deles com queda na taxa de filtração glomerular de 60 ml/min/1,73 m2 sc) e outro estava em diálise crônica. Complicações infecciosas graves ocorreram em 5 pacientes com RC e 2 com SC. Um paciente com DC e um com RC desenvolveram hipertensão arterial crônica. Em DC e RC, foi observada diferença significativa no escore Z do IMC e da estatura entre o início e o final do seguimento. Conclusões: a incidência calculada corresponde apenas ao setor da assistência pública de nosso país, não reflete a incidência global em nível nacional, sendo comparável a outras séries. A evolução dos pacientes com SC e RC também foi semelhante às descritas. O crescimento das crianças expostas ao tratamento com corticosteróides a longo prazo se afetou. Esses pacientes devem receber tratamento individualizado de acordo com as recomendações atuais para obter os melhores resultados.
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Resumen: Introducción: las infecciones respiratorias agudas bajas (IRAB) constituyen la principal causa de ingreso hospitalario en menores de 2 años. La utilización de cánula nasal de alto flujo (CNAF) es un instrumento terapéutico eficaz para evitar la ventilación invasiva, especialmente para los pacientes menores de 6 meses que constituyen el grupo de mayor riesgo. Objetivos: presentar la experiencia en la implementación de la terapia con CNAF en pacientes menores de 2 años con IRAB con insuficiencia respiratoria tratados en un sector de internación de infecciones respiratorias virales y analizar la población derivada a sectores de mayor complejidad. Pacientes y método: estudio observacional prospectivo en el que se incluyeron pacientes menores de 2 años con IRAB e insuficiencia respiratoria que recibieron tratamiento con CNAF, desde el 1° de junio al 31 de agosto del 2015 en un sector de internación del Hospital Pediátrico del Centro Hospitalario Pereira Rossell (HP/CHPR) de Montevideo, Uruguay. Resultados: se incluyeron 125 pacientes, 47 niñas y 78 varones, con una mediana de edad de 3 meses (16 días - 24 meses). En el 53% de ellos se identificó VRS. La duración de la terapia con CNAF tuvo una mediana de 69 horas (4 - 192 horas). La mediana del score de TAL modificado previo a su utilización fue de 7 (rango 5 - 9) y a las dos horas de 5 (rango 3 - 8). La terapia con CNAF se acompañó de una reducción significativa de la frecuencia cardíaca (FC). No se observaron efectos adversos ni complicaciones por la técnica. Requirieron ingreso a sectores de mayor complejidad (unidad de cuidados intensivos UCI o cuidados respiratorios especiales agudos CREA) el 38% (n=47), de los cuales el 36% (n=17) requirió asistencia ventilatoria mecánica invasiva (AVMI), el 25% (n=12) ventilación no invasiva (VNI) y el 38% (n=18) continuó recibiendo tratamiento con CNAF. Los menores de 3 meses requirieron derivación a sectores de mayor complejidad con más frecuencia (p=0,0036). Conclusiones: la utilización de CNAF pudo ser implementada sin complicaciones en una sala de internación pediátrica. El 62% de los pacientes no requirió otro tipo de apoyo respiratorio. Los menores de 3 meses requirieron traslado a cuidados críticos con mayor frecuencia.
Summary: Introduction: acute lower respiratory infections (LRTI) are the leading cause of hospitalization in children under 2 years of age. High-Flow Oxygen (HFO) is a highly effective method to prevent invasive ventilation, even for patients under 6 months of age, the highest-risk group. Objective: to present our experience and results for patients under 2 years of age with LRTI and moderate or severe respiratory distress treated with HFO and to analyze the subgroup of patients that needed to be transferred to other hospital units to continue their treatment. Patients and method: patients under 2 years of age with LRTI and respiratory failure who required HFO were included in a prospective observational study carried out between June 1 and August 31, 2015 at the Inpatient Area of the Pediatric Hospital, Centro Hospitalario Pereira Rossell (PH/CHPR), Montevideo, Uruguay. Results: 125 patients were included. 47 girls and 78 boys with a median age of 3 months (16 days-24 months). 53% of them were RSVs positive. The median connection time was 69 hours (Range 4 -192). The median for the modified TAL score was 7 (Range 5-9) and 5 (Range 3-8) before connection and 2 hours later respectively. HFO resulted into a significant reduction of heart rate. No adverse effects or complications were observed. 38% (n = 47) of patients were transferred to intensive care or special acute respiratory care but just a 36% (n = 17) of them needed mechanical ventilation and 25.5% (n = 12) needed non-invasive ventilation (NIV); the remaining 18 patients continued receiving HFO. Patients under 3 months of age needed to be transferred to ICU more often than older ones (p = 0.0036) Conclusions: the HFO technique could be implemented without complications in pediatric units. 62% of patients did not need additional respiratory support. Patients under 3 months of age needed to be transferred to Intensive Care more often than older patients.
Resumo: Introdução: as infecções respiratórias agudas inferiores (IRA) são a principal causa de hospitalização em crianças menores de 2 anos. O oxigênio de alto fluxo (OAF) é um método altamente eficaz para prevenir a ventilação invasiva, mesmo em pacientes com menos de 6 meses de idade, o grupo de maior risco. Objetivo: apresentar nossa experiência e resultados nos pacientes com menos de 2 anos de idade com IRA com dificuldade respiratória moderada ou grave tratados com OAF e analisar o subgrupo de pacientes que precisaram ser transferidos para outras áreas hospitalares para continuar o seu tratamento. Pacientes e método: pacientes com menos de 2 anos de idade com ITRI e insuficiência respiratória que necessitaram de OAF foram incluídos em um estudo observacional prospectivo realizado entre 1 de junho e 31 de agosto de 2015 na Área de Internação do Hospital Pediátrico, Centro Hospitalario Pereira Rossell (PH / CHPR), Montevidéu, Uruguai. Resultados: 125 pacientes foram incluídos. 47 meninas e 78 meninos com idade média de 3 meses (16 dias a 24 meses). 53% deles foram positivos para o VSR. O tempo médio de conexão foi de 69 horas (Faixa 4 -192). A mediana do escore TAL modificado foi de 7 (intervalo 5-9) e 5 (intervalo 3-8) antes da conexão e 2 horas depois, respectivamente. HFO resultou em uma redução significativa na frequência cardíaca. Não foram observados efeitos adversos ou complicações. 38% (n = 47) dos pacientes foram transferidos para tratamento intensivo ou respiratório agudo especial, mas apenas 36% (n = 17) deles necessitaram de ventilação mecânica e 25,5% (n = 12) necessitaram de ventilação não invasiva (VNI); os 18 pacientes restantes continuaram recebendo HFO. Pacientes com menos de 3 meses de idade precisaram ser transferidos para UTI mais frequentemente do que os outros (p = 0,0036) Conclusões: a técnica OAF poderia ser implementada sem complicações em unidades pediátricas. 62% dos pacientes não precisaram de suporte respiratório adicional. Pacientes com menos de 3 meses de idade precisaram ser transferidos para terapia intensiva com mais frequência do que pacientes mais velhos.
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El lupus eritematoso sistémico (LES) tiene una prevalencia baja en la población general y es menor en la edad pediátrica. La nefropatía lúpica (NL) es más frecuente y de mayor severidad que en adultos, condicionando la morbimortalidad de la enfermedad. Se realizó un estudio descriptivo prospectivo de 20 niños y adolescentes con NL controlados en la Policlínica de Colagenopatías del Centro Hospitalario Pereira Rossell en el período desde octubre de 2003 hasta setiembre de 2013 con el objetivo de describir las características clínico-serológicas y evolutivas de pacientes con NL y correlacionarlas con los hallazgos anátomopatológicos. La NL se observó en el 52,6% de los casos con LES. El 70% fueron de sexo femenino, relación femenino/masculino de 2,3/1, 85% de raza blanca, la mediana del diagnóstico fue de 12 años. Las formas de presentación fueron: alteraciones urinarias menores (AUM) en 14 pacientes (0,7), en cuatro casos síndrome nefrótico (SN), con o sin insuficiencia renal (IR) y/o hipertensión arterial. Un paciente se manifestó con síndrome nefrítico. Un paciente tenía un examen de orina normal. Las formas histopatológicas proliferativas graves se presentaron en 18 (0,9); los casos con AUM presentaban NL grado III-IV en 13 (0,93); todos los casos con SN con o sin IR tenían NL III-IV. No hubo casos de NL aislada como forma de comienzo. En el momento del diagnóstico, los anticuerpos antinucleares fueron positivos en 19 (0,95) y los anti DNA doble cadena en 16 (0,8); C3 y C4 estuvieron descendidos en 19 (0,95) y en 15 (0,75) respectivamente. El seguimiento promedio fue 4,2 años. Al final del seguimiento estaban en remisión 16 pacientes (0,8), cuatro en remisión parcial, todos con función renal normal, excepto un caso que presentó IR extrema, fue trasplantado y tuvo una excelente evolución. Un paciente falleció con hemorragia pulmonar. La sobrevida de la función renal y la de los pacientes fue 0,95 respectivamente. El tratamiento se realizó en base a corticoides, hidroxicloroquina asociados a azatioprina o micofenolato mofetilo. En ocho pacientes con cuadros graves se usó la ciclofosfamida I/V. Esta serie constituye la primera serie nacional de nefropatía lúpica en niños y adolescentes. Conclusión: predominó la presentación clínica con AUM y formas histopatológicas severas, clases III y IV, evidenciando una disociación clínico anatomopatológica. A pesar del elevado porcentaje de NL severas, el manejo adecuado y oportuno y la adherencia al tratamiento y a los controles médicos fueron fundamentales para la evolución favorable de la NL.
Systemic lupus erythematosus (SLE) has a low prevalence in the overall general population and this is lower in children. Child lupus nephropathy (LN) is more frequent and severe than in SLE adult patients, with greater disease morbidity and mortality. A prospective descriptive study of 20 children and adolescents with LN monitored in the Collagen Diseases Office of the Pereira Rossell Hospital between October, 2003 and September, 2013 was performed. The objective of this study was to describe clinical-serological features and the evolution of these patients and to correlate them with its anatomopathological findings. LN was diagnosed in 52,6% of the SLE patients, 70% were female with a female/male correlation of 2,3/1; 85% were Caucasian; median age at diagnosis was 12 years old. The clinical presentations were minor urinary findings (MUF) in 14 patients (0,7) and nephrotic syndrome (NS) in 4 (0,2), and another one nephritic syndrome. One patient presented no symptoms and had normal urinalysis. Severe proliferative classes predominated in18 patients (0.9); 13 (0.93) patients with MUF and all the patients with NS had LN classes III or IV. Isolated LN was not seen in the initial presentation. At the time of diagnosis antinuclear antibodies were positive in 19 patients (0.95); and anti DNA double stranded in 16 (0.8). Low C3 was found in 19 (0.95) and C4 in 15 (0.75), respectively. Average follow-up time was 4.2 years. At the end of follow-up 16 (0.8) were in remission, 4 of them in partial remission; all patients presented normal renal function except for one who evidenced severe renal failure and required hemodialysis and transplantation and had an excellent evolution. One patient died with pulmonary hemorrhage. The renal and patient survivals were 0.95 respectively. Treatment consisted in corticosteroids and hydroxychloroquine associated with azathioprine or mycophenolate mofetil. Cyclophosphamide was administered to 8 patients with severe illness. This is the first national report of LN in children and adolescents. Conclusions: the predominant clinical presentation of LN was MUF with severe anatomopathological findings, classes III and IV, showing a clinical-pathological dissociation. Despite the high percentage of severe LN, early and adequate treatment, as well as a good compliance to it with periodic medical follow-up, were essential to achieve a favorable outcome of LN.
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Humanos , Masculino , Adolescente , Nefritis Lúpica , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Nefritis Lúpica/orina , Nefritis Lúpica/sangre , Insuficiencia Renal/etiologíaRESUMEN
La enfermedad litiásica puede comenzar en la infancia con manifestaciones escasas o atípicas. Su incidencia es menor que en adultos y es de difícil diagnóstico. La causa favorecedora (metabólica, infecciosa, malformativa, mixta) se encuentra con mayor frecuencia que en adultos. El objetivo es describir las características clínicas, la evolución y el tratamiento de los niños hospitalizados con litiasis urinaria en el CHPR.Se realizó un estudio descriptivo, retrospectivo entre el 1 de junio de 2006 y el 31 de mayo de 2012. Se incluyeron todos los niños de 1 mes a 14 años hospitalizados con diagnóstico de litiasis urinaria. Se analizó presentación clínica, causas predisponentes, tratamiento y evolución. La fuente de datos fueron las historias clínicas. Se hospitalizaron 20 niños, 12 varones y ocho mujeres, mediana 10,5 años. El dolor fue la presentación clínica más frecuente (n=17). La litiasis fue única en 11 casos y múltiple en 9. Se diagnosticó litiasis coraliforme con pionefrosis en dos niños y en otros dos nefrocalcinosis. Presentaron complicaciones obstructivas (n=15), infecciosas (n=4), insuficiencia renal aguda leve (n=3). Se hallaron causas predisponentes en 13 niños: metabólicas (n=9), infecciosas (n=4), malformativas (n=3); el estudio metabólico se realizó en 10 casos, siendo completo en tres de ellos. Recibieron tratamiento quirúrgico o litotricia 10 pacientes. Los niños con litiasis coraliforme y pionefrosis requirieron nefrectomía. Permanecen en seguimiento seis niños: tres persisten con litiasis y dos tienen nefrocalcinosis, uno de ellos con IRC moderada.Esta constituye la primera comunicación de litiasis urinaria en niños hospitalizados. Aunque se trata de un centro de referencia nacional, conocer la prevalencia y características de esta enfermedad requiere estudios multicéntricos. Una proporción importante de niños presentó complicaciones graves...
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Urolitiasis/complicaciones , Urolitiasis/diagnóstico , Urolitiasis/etiología , Urolitiasis/terapia , Niño Hospitalizado , Enfermedades MetabólicasRESUMEN
Resumen La enfermedad ósea que se expresa como raquitismo deriva de diferentes desórdenes, desde la carencia de vitamina D, síndromes malabsortivos, enfermedad renal crónica, displasia metafisaria, hipofosfatasia y raquitismos resistentes, dentro de los cuales están los hipofosfatémicos y aquellos vitamina D dependientes. Presentamos una paciente de 2 años y 6 meses, con síntomas y signos de un raquitismo activo, hipocalcemia severa asintomática, normofosforemia, aumento de la fosfatasa alcalina y de la hormona paratiroidea y con niveles normales de 25 hidroxi vitamina D en sangre. Se diagnosticó como un probable raquitismo vitamina D dependiente tipo I dada la respuesta satisfactoria y rápida con calcio y 0,5 microgramos/día de calcitriol por vía oral.
Summary Rickets is a disease which disturbs normal bone formation through different methods, like vitamin D deficiency, malabsorption, chronic renal disease, metaphisary dysplasia, low phosphorus and resistant rickets. A two and a half year old patient with active rickets who had asymptomatic severe hypocalcemia, normal phosphorus level, high alkaline phosphatase and high parathyroid hormone and normal serum 25- hydroxycholecalciferol. Probable vitamin D dependence type I rickets was diagnosed due to her rapid recovery with the treatment given.