Somatic Mosaicism for Paternal Uniparental Disomy of 11p15.5 Region in Adrenal and Liver Tissues in a Newborn with Atypical Beckwith-Wiedemann Syndrome.

Beckwith-Wiedemann syndrome (BWS) is characterized by overgrowth and increased risk of embryonic tumors. It results from alterations in genes controlled by imprinting centers H19DMR (Imprinting Center [IC] 1) and KvDMR (IC2). Strategies for diagnostic confirmation include methylation analysis and CDKN1C sequencing. We present a newborn with placentomegaly, hyperinsulinism and adrenal cytomegaly, but no typical external features of BWS. The patient had normal genetic studies in blood. However, adrenal and liver tissues showed hypermethylation of IC1 and hypomethylation of IC2. Microsatellite analysis confirmed mosaic paternal uniparental disomy. This study demonstrates the importance of analyzing additional tissues to reduce underdiagnosis of somatic mosaicism in BWS.

[Pseudohypoparathyroidism: report of two cases of late presentation]. / Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos.

Pseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyperphosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth's Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting, they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroidism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism.

Serum Cortisol and Cortisone as Potential Biomarkers of Partial 11ß-Hydroxysteroid Dehydrogenase Type 2 Deficiency.

BACKGROUND: Pathogenic variations in HSD11B2 gene triggers the apparent mineralocorticoid excess syndrome (AME). There is scarce information regarding the phenotypes of subjects carrying heterozygous pathogenic variants in HSD11B2 gene. We investigated if serum cortisol/cortisone (F/E) ratio and cortisone are useful for identifying partial 11ßHSD2 deficiency in those heterozygous subjects. METHODS: We studied two patients diagnosed with AME and their families carrying either D223N or R213C mutation. We also evaluated 32 healthy control subjects (13 children and 19 adults) to obtain normal references ranges for all measured variables. Case 1: A boy carrying D223N mutation in HSD11B2 gene and Case 2: A girl carrying R213C mutation. We assessed serum F/E ratio and cortisone by HPLC-MS/MS, aldosterone, plasma-renin-activity(PRA), electrolytes, and HSD11B2 genetic analyses. RESULTS: The normal values (median [interquartile range]) in children for serum F/E and cortisone (µg/dl) were 2.56 [2.21-3.69] and 2.54 [2.35-2.88], and in adults were 4.42 [3.70-4.90] and 2.23 [1.92-2.57], respectively. Case 1 showed a very high serum F/E 28.8 and low cortisone 0.46 µg/dl. His mother and sister were normotensives and heterozygous for D223N mutation with high F/E (13.2 and 6.0, respectively) and low cortisone (2.0 and 2.2, respectively). Case 2 showed a very high serum F/E 175 and suppressed cortisone 0.11 µg/dl. Her parents and sister were heterozygous for the R213C mutation with normal phenotype, but high F/E and low cortisone. Heterozygous subjects showed normal aldosterone, PRA, but lower fractional excretion of sodium and urinary Na/K ratio than controls. CONCLUSION: Serum F/E ratio and cortisone allow to identify partial 11ßHSD2 deficiencies, as occurs in heterozygous subjects, who would be susceptible to develop arterial hypertension.

Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos / Pseudohypoparathyroidism: report of two cases of late presentation

Pseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyperphosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth's Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting, they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroidism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism.

[Fever of unknown origin: a challenge for the pediatric infectious diseases specialist]. / Síndrome febril prolongado: un desafío para el infectólogo pediatra.

INTRODUCTION: Prolonged febrile syndrome (PFS) is defined as fever 7-10 days, with initial study does not allow etiologic diagnosis. OBJECTIVE: To describe the main causes of the PFS and its temporal behavior in Pediatric Infectious Diseases Unit Outpatient Care of Complejo Asistencial Dr. Sótero del Río (CASR). PATIENTS AND METHODS: A descriptive, prospective study between january 2007-december 2012, about 153 patients from 6 weeks to 14 years 11 months old, diagnosed with PFS, tab completing clinical and laboratory monitoring. RESULTS: etiology was obtained in 67.9%, the causes were infection (88.4%), neoplasms (4.8%), rheumatological (4.8%) and Kawasaki disease (2.8%). The most important infectious causes were enteric fevers (typhoid and paratyphoid) (18.4%), urinary tract infection (11.9%), Bartonella henselae infections and adenovirus (8.7%) each one and Epstein Barr virus (7.6%). Ninety eight percent of patients had complete resolution, 60.7% did not require hospitalization and mortality was 0%. DISCUSSION: As in previous pediatric clinical series the infections were the most frequent causes. Enteric fever persists as principal cause, however, the epidemiological evidence is oscillating in time endorsing the local statistics can count over the years to improve the diagnostic and therapeutic approach.

Síndrome febril prolongado: un desafío para el infectólogo pediatra / Fever of unknown origin: a challenge for the pediatric infectious diseases specialist

Introduction: Prolonged febrile syndrome (PFS) is defined as fever 7-10 days, with initial study does not allow etiologic diagnosis. Objective: To describe the main causes of the PFS and its temporal behavior in Pediatric Infectious Diseases Unit Outpatient Care of Complejo Asistencial Dr. Sótero del Río (CASR). Patients and Methods: A descriptive, prospective study between january 2007-december 2012, about 153 patients from 6 weeks to 14 years 11 months old, diagnosed with PFS, tab completing clinical and laboratory monitoring. Results: etiology was obtained in 67.9%, the causes were infection (88.4%), neoplasms (4.8%), rheumatological (4.8%) and Kawasaki disease (2.8%). The most important infectious causes were enteric fevers (typhoid and paratyphoid) (18.4%), urinary tract infection (11.9%), Bartonella henselae infections and adenovirus (8.7%) each one and Epstein Barr virus (7.6%). Ninety eight percent of patients had complete resolution, 60.7% did not require hospitalization and mortality was 0%. Discussion: As in previous pediatric clinical series the infections were the most frequent causes. Enteric fever persists as principal cause, however, the epidemiological evidence is oscillating in time endorsing the local statistics can count over the years to improve the diagnostic and therapeutic approach.

Introducción: El síndrome febril prolongado (SFP) se define como fiebre entre 7-10 días, con estudio inicial que no permite un diagnóstico etiológico. Objetivo: Describir las principales etiologías del SFP y su comportamiento temporal en la unidad de infectología pediátrica ambulatoria del Complejo Asistencial Dr. Sótero del Río (CASR). Pacientes y Método: Estudio descriptivo, prospectivo, entre enero de 2007-diciembre de 2012. Análisis de 153 pacientes entre 6 semanas y 14 años 11 meses de edad, con diagnóstico de SFP, que completaron ficha de seguimiento clínico-laboratorial. Resultados: Se obtuvo diagnóstico etiológico en 67,9%, las causas fueron: infecciones (88,4%), neoplasias (4,8%), reumatológicas (4,8%) y enfermedad de Kawasaki (2,8%). Las causas infecciosas más importantes fueron: fiebres entéricas (tifoidea y paratifoidea) (18,4%), infección del tracto urinario (11,9%), enfermedades por Bartonella henselae y adenovirus (8,7%) cada uno y virus de Epstein Barr (7,6%). El 98% de los pacientes tuvo resolución completa, 60,7% no requirió hospitalización y no se registraron decesos. Discusión: Como en las series clínicas antes publicadas, las infecciones fueron la causa más frecuente de SFP. La fiebre entérica persiste como causa principal; sin embargo, se evidencia una situación epidemiológica oscilante en el tiempo justificando la necesidad de contar con estadísticas locales a lo largo de los años para mejorar el enfoque diagnóstico y terapéutico.

Efectividad de la vacuna antivaricela como profilaxis post exposición en niños chilenos / Effectiveness of varicella vaccine as post exposure prophylaxis in Chilean children

Introduction: Efficacy and effectiveness of varicella vaccine (VV) as post exposure prophylaxis (PEP) strategy have shown discordant results for disease risk reduction, and more consistent results in their ability to attenuate the disease. Aim: To assess the effectiveness of VV as PEP among household contacts. Material and Methods: We followed up 33 children after household exposure to a varicella case, of which 15 received VV as PEP and 18 did not received VV. The presence and severity of the disease were clinically determined. Results: Secondary attack rate was 53% among vaccinated and 89% among non-vaccinated children. Overall effectiveness of VV as PEP was 40% (CI95% 1%-64%). The effectiveness for preventing moderate or severe disease was 63% (CI95% 8%-85%) in the entire group and 77% (CI95% 14%-94%) among children vaccinated during the first 3 days post exposure. Vaccine tolerance was acceptable, with a low number of adverse reactions, all of them mild. Conclusion: The results suggest that VV as PEP is effective among household contacts, especially for reducing the severity of the disease.

Introducción: Los estudios de eficacia y efectividad de la vacuna antivaricela (V AV) como profilaxis post exposición (PPE) han mostrado resultados disímiles en cuanto a la reducción del riesgo de enfermar, y algo más consistentes en su capacidad de atenuar la enfermedad. Objetivo: Evaluar la efectividad de la VAV como PPE utilizada en contactos domiciliarios. Material y Métodos: Se realizó el seguimiento post exposición de 33 contactos domiciliarios de casos de varicela, de los cuales 15 recibieron VAV como PPE y 18 no la recibieron. Se determinó clínicamente el desarrollo de enfermedad y la intensidad de la misma. Resultados: La tasa de ataque secundario fue 53% en vacunados y 89% en no-vacunados, siendo la efectividad global de la VAV como PEP 40% (IC95% 1%-64%). La efectividad para prevenir enfermedad moderada o intensa fue 63% (IC95% 8-85%) en el grupo completo y 77% (IC95% 14-94%) en los niños vacunados durante los primeros tres días post exposición. La tolerancia a la vacuna fue aceptable, con un bajo número de reacciones adversas, todas leves. Conclusión: Los resultados sugieren que la VAV es efectiva como PPE en contactos domiciliarios, especialmente para reducir la intensidad de la enfermedad.

[Effectiveness of varicella vaccine as post exposure prophylaxis in Chilean children]. / Efectividad de la vacuna antivaricela como profilaxis post exposición en niños chilenos.

INTRODUCTION: Efficacy and effectiveness of varicella vaccine (VV) as post exposure prophylaxis (PEP) strategy have shown discordant results for disease risk reduction, and more consistent results in their ability to attenuate the disease. AIM: To assess the effectiveness of VV as PEP among household contacts. MATERIAL AND METHODS: We followed up 33 children after household exposure to a varicella case, of which 15 received VV as PEP and 18 did not received VV. The presence and severity of the disease were clinically determined. RESULTS: Secondary attack rate was 53% among vaccinated and 89% among non-vaccinated children. Overall effectiveness of VV as PEP was 40% (CI95% 1%-64%). The effectiveness for preventing moderate or severe disease was 63% (CI95% 8%-85%) in the entire group and 77% (CI95% 14%-94%) among children vaccinated during the first 3 days post exposure. Vaccine tolerance was acceptable, with a low number of adverse reactions, all of them mild. CONCLUSION: The results suggest that VV as PEP is effective among household contacts, especially for reducing the severity of the disease.