Mutación heterocigota, autosómica recesiva del gen RARS2 en una paciente colombiana de padres no consanguíneos / Autosomal recessive heterocygote mutation of the RARS2 gene in a colombian patient with non- consanguineous parents

Las nuevas metodologías de secuenciación masiva han permitido caracterizar e identificar variantes genéticas asociadas a diferentes patologías. En este trabajo se presenta el caso de una paciente con una mutación del gen RARS2 que codifica la enzima arginino-ARNt ligasa para la codificación de proteínas. Esta alteración genética se manifiesta en hipoplasia pontocerebelosa tipo 6, con una prevalencia de <1/1 000 0000, caracterizada por un cerebelo y un puente de menor tamaño asociados a un retraso grave en el neurodesarrollo. El análisis de caso permite un mejor conocimiento de enfermedades de origen genético, específicamente, de aquellas con patrones de herencia autosómicos recesivos de padres no consanguíneos. Su estudio sobre todo en lo relacionado con el ámbito familiar y socioeconómico, y su base genética, ayuda a una mejor calidad de vida de los pacientes y su familia.

The latest method of next-generation sequencing has allowed the characterization and identification of genetic variants associated to diverse pathologies. In this article, we present the case of female patient with a mutation of the RARS2 gene that encodes the enzyme for arginyl tRNA synthetase for coding of proteins. This genetic alteration manifests in pontocerebellar hypoplasia type 6, with a prevalence of <1/1,000,0000, characterized by a cerebellum and pons that are smaller in size and are associated with severe neurodevelopmental delay. The analysis of the case of this patient provides better knowledge of diseases of genetic origin; specifically, regarding genetic diseases of autosomal recessive patterns of inheritance from non-consanguineous parents. The impact of these studies; specially within the family, social, economic and genetic aspects helps provide a better quality of life for these patients and their family.

Late diagnosis of pseudohypoparathyroidism in adulthood. Case series / Pseudohipoparatiroidismo diagnosticado tardíamente en la adultez, una serie de casos

Abstract Introduction: Pseudohypoparathyroidism (PHP) is a rare hereditary disease, characterized by hypocalcemia/hyperphosphatemia secondary to peripheral resistance to parathyroid hormone (PTH). PHP diagnosis is usually precluded since hypocalcemia is considered as the primary diagnosis, thus delaying further diagnostic studies and preventing an adequate management of this clinical condition. Materials and methods: Retrospective review of the databases of the Endocrinology departments of two tertiary care centers of Medellin, Colombia from January 2012 to December 2016. Patients diagnosed with PHP based on clinical presentation and confirmatory laboratory values were included. Results: Four patients met the inclusion criteria. All PHP cases were diagnosed in adulthood despite strong early clinical and laboratory evidence of the disease. Three patients were diagnosed with Fahr's syndrome and two with Albright's hereditary osteodystrophy. The mean values obtained were PTH of 376.8 pg/mL, calcium of 6.17 mg/dL and phosphorus of 6.55 mg/dL. Conclusions: PHP is a rare disorder. This paper describes four PHP cases diagnosed during adulthood. Emphasis should be placed on the judicious approach to the patient with hypocalcemia and hyperphosphatemia with increased PTH and normal renal function, since these symptoms strongly suggest a diagnosis of PHP.

Resumen Introducción. El pseudohipoparatiroidismo (PHP) es una condición rara caracterizada por hipocalcemia e hiperfosfatemia secundarias a resistencia periférica a la hormona paratiroidea (PTH). Es frecuente que la hipocalcemia sea establecida de forma equivocada como diagnóstico primario y que el diagnóstico definitivo de PHP sea tardío, difiriendo los estudios y el manejo específico que exigen estos pacientes. Materiales y métodos. Se revisaron de forma retrospectiva las bases de datos de endocrinología de dos centros terciarios de Medellín, Colombia, desde enero de 2012 a diciembre de 2016. Se incluyeron pacientes con diagnóstico de PHP por presentación clínica y valores confirmatorios de laboratorio. Resultados. Cuatro pacientes cumplieron los criterios de inclusión. Todos los casos fueron diagnosticados en la adultez a pesar de tener evidencia temprana, clínica y bioquímica de la enfermedad. Tres pacientes tenían síndrome de Fahr y dos tenían osteodistrofia hereditaria de Albright. Los valores medios registrados fueron PTH de 376.8 pg/mL, calcio de 6.17 mg/dL y fósforo de 6.55 mg/dL. Conclusiones. El PHP es un trastorno raro; se describen cuatro casos diagnosticados de forma tardía en la adultez. Se enfatiza en el enfoque juicioso del paciente con hipocalcemia, la cual, en presencia de hiperfosfatemia con PTH elevada y función renal normal, debe hacer sospechar el diagnóstico de PHP.

Resultados del tratamiento multidisciplinario de tumores neuroendocrinos de intestino delgado / Outcomes of multidisciplinary treatment of neuroendocrine tumors of the small intestine

Resumen Objetivos: Describir los resultados del tratamiento de pacientes con tumores neuroendocrinos (TNE) del intestino delgado tratados por un grupo multidisciplinario. Métodos: Estudio tipo serie de casos en pacientes con diagnóstico histológico confirmado de tumor neuroendocrino con primario intestinal entre el 1 de mayo de 2004 y el 30 de abril de 2014. Resultados: En el periodo del estudio se atendieron en la institución 301 pacientes con diagnóstico de TNE de diferentes localizaciones, de los cuales 48 casos de primario intestinal reunieron los criterios de inclusión. La cirugía con intención curativa o paliativa fue la primera línea de tratamiento en la mayoría de pacientes (n = 35; 72,9%) y se logró remisión completa en 13 de ellos. Los análogos de somatostatina fueron la primera línea de manejo en el 14,5%. Al momento de la última valoración: 13 pacientes (27,1%) estaban libres de enfermedad; 17 pacientes (35,4%) se encontraban estables, y 7 pacientes (14,6%) con enfermedad en progresión. Más del 50% de los pacientes permanecieron vivos a los 5 años luego del diagnóstico. La mayor edad al momento del diagnóstico, la presencia de síndrome carcinoide, el compromiso metastásico, el grado histológico, y los valores elevados de marcadores bioquímicos (cromogranina A y 5-hidróxi indol ácido acético), fueron factores que se encontraron asociados a un peor pronóstico de supervivencia. Conclusiones: En el presente artículo se resumen los resultados clínicos del tratamiento de los pacientes con TNE de primario intestinal en un grupo multidisciplinario y la confrontación de dichos resultados con los datos disponibles en la literatura.

Abstract Aim: To describe the outcomes in a group of patients with neuroendocrine tumors (NETs) of the small intestine treated in a multidisciplinary group. Methods: A descriptive study based on the clinical records of patients with confirmed histological diagnosis of a neuroendocrine tumor with intestinal primary between 1 May 2004 and 30 April 2014 Results: A total of 301 patients diagnosed with NETs in different locations were treated during the study period, of which 48 cases of intestinal primary met the inclusion criteria. Surgery with curative or palliative intent was the first line of treatment in most patients (n = 35, 72.9%) and complete remission was achieved in 13 of them. Somatostatin analogues were the first line of management in 14.5%. At the time of the last assessment, 13 patients (27.1%) remained disease-free, 17 patients (35.4%) with persistent but stable disease, and 7 patients (14.6%) had progressive disease. More than 50% of the patients remained alive at 55 months after diagnosis. The higher age at diagnosis, the presence of carcinoid syndrome, the metastatic compromise, the histological grade, and elevated biochemical markers (Chromogranin A and 5-hydroxy indole acetic acid) were factors associated with a worse survival prognosis. Conclusions: A summary is presented on the clinical outcomes of the treatment of patients with NET of primary intestinal by a multidisciplinary group, as well as the comparison of these outcomes with the data available in the literature.

Niveles de fosfolipasa A2 asociada a lipoproteína en sujetos sin enfermedad coronaria con riesgo cardiovascular variable / Association of lipoprotein-associated phospholipase activity A2 with cardiovascular risk factors

Background:Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker involved in atherosclerosis and directly associated with cardiovascular events. Aim: To determine Lp-PLA2 levels in asymptomatic subjects with differing cardiovascular risk. Material and Methods: We studied 152 subjects aged 46 ± 11 years (69 women). We recorded traditional cardiovascular risk factors, creatinine, ultrasensitive C-reactive protein, fibrinogen, fasting lipids, blood sugar and activity levels of Lp-PLA2. Cardiovascular risk was classified according to the number of risk factors of each subject (0,1-2 or ≥ 3 risk factors). Besides, we calculated global Framingham risk score. Results: The average Framingham score of participants was 6%. Twenty percent of participants had no risk factors, 46% had 1 or 2 and 34% had ≥ 3. Mean Lp-PLA2 levels were 185 ± 48 nmol/ml/min (201 ± 49 in men and 166 ± 38 in women). Lp-PLA2 correlated significantly (p < 0,05 for all) with non-HDL cholesterol, LDL, HDL, creatinine, waist circumference, body mass index and Framingham risk score. There was no correlation with blood sugar, C-reactive protein, fibrinogen or smoking status. Lp-PLA2 levels were significantly higher according to the number of risk factors: 0 factors: 163 ± 43, 1-2 factors: 185 ± 45 and ≥ 3 factors: 201 ± 47 nmol/ml/min, respectively. Linear regression analysis showed that the best predictor of Lp-PLA2 was non-HDL cholesterol (β= 0,74; p < 0,0001). Conclusions: Lp-PLA2 activity increased along with the number of cardiovascular risk factors and was correlated mainly with non -HDL cholesterol.

Exit: tratamiento exútero intraparto: reporte de caso y revisión de la literatura / Exit: ex-utero intrapartum treatment: a case report and literature review

Introducción y objetivo: la técnica Tratamiento exútero intraparto (EXIT) permite el aseguramiento de la vía aérea fetal mientras se mantiene el soporte uteroplacentario íntegro. El objetivo de reportar este caso es describir el procedimiento y hacer una revisión de la literatura mundial respecto a consideraciones anestésicas y complicaciones asociadas. Materiales y métodos: presentamos el caso de una neonato femenina de 39 semanas de gestación que nace mediante la técnica Tratamiento exútero intraparto (EXIT) debido a una potencial obstrucción de la vía aérea detectada en una ecografía de tercer trimestre. Se realizó una búsqueda sistemática usando las palabras clave: Tratamiento exútero intraparto (EXIT), masas cervicales congénitas y CHAOS en las bases de datos Medline via Pub Med, Ovid, y la base latinoamericana SciELO. Resultados: se encontraron un total de 183 artículos, de los cuales 76 estaban relacionados directamente con el tema, de estos se seleccionaron 8 reportes de caso, 2 series de casos y 14 revisiones del tema. Conclusiones: la estrategia EXIT prueba ser una herramienta útil en el adecuado manejo de los neo-natos con obstrucciones congénitas de la vía aérea.

Introduction and objective: The EXIT procedure (ex-utero intrapartum treatment) is aimed at securing the fetal high airway whilst maintaining integral uteroplacentary circulation. The purpose of reporting this case was to describe the procedure and review the worldwide literature regarding anesthetic considerations and associated complications. Materials and methods: The case of a 39-week gestation female neonate is presented; she was born at the Clínica del Country (a private highlevel healthcare general hospital located in Bogota, Colombia) by the ex-utero intrapartum treatment (EXIT) technique due to a potential obstruction of the airway detected during third-trimester echography. A systematic search was made of Medline databases via PubMed, Ovid, and the SciELO Latin-American database using the following key words: EXIT, ex-utero intrapartum treatment, congenital cervical mass, CHAOS. Results: 183 articles were found, of which 76 were directly related to the topic; 8 case reports, 2 case series and 14 reviews of the topic were selected. Conclusion: The EXIT strategy has proved to be a useful tool in the suitable management of neonates suffering congenital obstruction of the airway.