RESUMEN

OBJECTIVE: This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. METHODS: A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. RESULTS: Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. CONCLUSION: This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.

Asunto(s)

Cardiomiopatía Hipertrófica , Humanos , Femenino , Masculino , Adulto , Estudios de Seguimiento , Adulto Joven , Persona de Mediana Edad , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/complicaciones , Brasil/epidemiología , Adolescente , Mutación , Proteínas Quinasas Activadas por AMP/genética , Fenotipo , Niño , Arritmias Cardíacas/genética , Arritmias Cardíacas/etiología , Síndrome , Anciano

RESUMEN

ABSTRACT Objective This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. Methods A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. Results Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. Conclusion This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.

RESUMEN

Resumen Actualmente hay un porcentaje importante de autopsias que quedan sin un diag nóstico concluyente del fallecimiento, especialmente cuando este evento letal se produce súbitamente. El análisis genético se ha ido incorporando recientemente al campo de la medicina forense, sobre todo en aquellos pacientes que han fallecido de forma repentina, y donde no se identifica causa concluyente del fallecimiento tras una autopsia médico-legal completa. En estos casos las enfermedades eléctricas primarias son las principales responsables del fallecimiento. Hasta la fecha se han descrito más de 40 genes asociados a afecciones arritmogénicas causantes de muerte súbita cardiaca. Las principales enfermedades arritmogénicas son el síndrome de QT largo y la taquicardia ventricular; estudios genéticos post-mortem no solo permiten llevar a cabo un diagnóstico de la causa del fallecimiento, sino que también permiten una traslación clínica hacia los familiares, focalizado en la identificación precoz de individuos en riesgo de síncope, así como adopción de medidas terapéuticas personalizadas para la prevención de un episodio arrítmico letal.

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Abstract Currently, there are a significant percentage of autopsies left without a conclusive diagnosis of death, especially when this lethal event occurs suddenly. Genetic analysis has been recently incorporated into the field of forensic medicine, especially in patients with sudden death and where no conclusive cause of death is identified after a complete medical- legal autopsy. Inherited arrhythmogenic diseases are the main cause of death in these cases. To date, more than 40 genes have been associated with arrhythmogenic disease, and causing sudden cardiac death has been described. The main arrhythmogenic diseases are Long QT Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, Brugada Syndrome, and Short QT Syndrome. These post-mortem genetic studies, not only allow a diagnosis of the cause of death, but also allow a clinical translation in relatives, focusing on the early identification of individuals at risk of syncope, as well as adopting personalised therapeutic measures for the prevention of a lethal arrhythmic episode.

Asunto(s)

Humanos , Arritmias Cardíacas/complicaciones , Autopsia/métodos , Muerte Súbita Cardíaca/etiología , Arritmias Cardíacas/genética , Síncope/etiología

RESUMEN

Currently, there are a significant percentage of autopsies left without a conclusive diagnosis of death, especially when this lethal event occurs suddenly. Genetic analysis has been recently incorporated into the field of forensic medicine, especially in patients with sudden death and where no conclusive cause of death is identified after a complete medical-legal autopsy. Inherited arrhythmogenic diseases are the main cause of death in these cases. To date, more than 40 genes have been associated with arrhythmogenic disease, and causing sudden cardiac death has been described. The main arrhythmogenic diseases are Long QT Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia, Brugada Syndrome, and Short QT Syndrome. These post-mortem genetic studies, not only allow a diagnosis of the cause of death, but also allow a clinical translation in relatives, focusing on the early identification of individuals at risk of syncope, as well as adopting personalised therapeutic measures for the prevention of a lethal arrhythmic episode.

Asunto(s)

Arritmias Cardíacas/complicaciones , Autopsia/métodos , Muerte Súbita Cardíaca/etiología , Arritmias Cardíacas/genética , Humanos , Síncope/etiología

RESUMEN

BACKGROUND PRKAG2 syndrome diagnosis is already well-defined as Wolff-Parkinson-White syndrome (WPW), ventricular hypertrophy (VH) due to glycogen accumulation, and conduction system disease (CSD). Because of its rarity, there is a lack of literature focused on the treatment. The present study aimed to describe appropriate strategies for the treatment of affected family members with PRKAG2 syndrome with a long follow-up period. CASE REPORT We studied 60 selected individuals from 84 family members (32 males, 53.3%) (mean age 27±16 years). Patients with WPW and/or VH were placed in a group of 18 individuals, in which 11 (61.1%) had VH and WPW, 6 (33.3%) had isolated WPW, and 1 (5.6%) had isolated VH. Palpitations occurred in 16 patients (88.9%), chest pain in 11 (61.1%), dizziness in 13 (72.2%), syncope in 15 (83.3%), and dyspnea in 13 (72%). Sudden cardiac death (SCD) occurred in 2 (11.1%), and 2 patients with cardiac arrest (CA) had asystole and pre-excited atrial flutter-fibrillation (AFL and AF) as the documented mechanism. Transient ischemic attack (TIA) and learning/language disabilities with delayed development were observed. Genetic analysis identified a new missense pathogenic variant (p.K290I) in the PRKAG2 gene. Cardiac histopathology demonstrated the predominance of vacuoles containing glycogen derivative and fibrosis. The treatment was based on hypertension and diabetes mellitus (DM) control, antiarrhythmic drugs (AD), anticoagulation, and radiofrequency catheter ablation (RCA). Six patients (33.3%) underwent pacemaker implantation (PM). CONCLUSIONS The present study describes the clinical treatment for a rare cardiac syndrome caused by a PRKAG2 mutation.

Asunto(s)

Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Derecha/etiología , Linaje , Síndrome de Wolff-Parkinson-White/genética , Proteínas Quinasas Activadas por AMP/genética , Aborto Espontáneo/etiología , Adulto , Arritmias Cardíacas/etiología , Trastorno Autístico/etiología , Brasil , Preescolar , Muerte Súbita Cardíaca/etiología , Discapacidades del Desarrollo/etiología , Mareo/etiología , Disnea/etiología , Femenino , Paro Cardíaco/etiología , Humanos , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Derecha/patología , Ataque Isquémico Transitorio/etiología , Trastornos del Desarrollo del Lenguaje/etiología , Masculino , Mutación Missense , Síncope/etiología

RESUMEN

BACKGROUND PRKAG2 syndrome diagnosis is already well-defined as Wolff-Parkinson-White syndrome (WPW), ventricular hypertrophy (VH) due to glycogen accumulation, and conduction system disease (CSD). Because of its rarity, there is a lack of literature focused on the treatment. The present study aimed to describe appropriate strategies for the treatment of affected family members with PRKAG2 syndrome with a long follow-up period. CASE REPORT We studied 60 selected individuals from 84 family members (32 males, 53.3%) (mean age 27±16 years). Patients with WPW and/or VH were placed in a group of 18 individuals, in which 11 (61.1%) had VH and WPW, 6 (33.3%) had isolated WPW, and 1 (5.6%) had isolated VH. Palpitations occurred in 16 patients (88.9%), chest pain in 11 (61.1%), dizziness in 13 (72.2%), syncope in 15 (83.3%), and dyspnea in 13 (72%). Sudden cardiac death (SCD) occurred in 2 (11.1%), and 2 patients with cardiac arrest (CA) had asystole and pre-excited atrial flutter-fibrillation (AFL and AF) as the documented mechanism. Transient ischemic attack (TIA) and learning/language disabilities with delayed development were observed. Genetic analysis identified a new missense pathogenic variant (p.K290I) in the PRKAG2 gene...

Asunto(s)

Hipertrofia , Síndrome de Wolff-Parkinson-White

RESUMEN

Relata-se o caso de paciente do sexo masculino portador de síndrome de Wolff-Parkinson-White,hipertrofia ventricular e doença do sistema de condução, que apresentou duas paradas cardiorrespiratórias,insuficiência cardíaca congestiva e uma nova variação no gene PRKAG2.

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We report the case of a male patient suffering from Wolff-Parkinson-White syndrome, ventricularhypertrophy, cardiac conduction system disease, who presented two cardiorespiratory arrests, congestive heartfailure and a new variation in the PRKAG2 gene.

Asunto(s)

Humanos , Masculino , Adolescente , Paro Cardíaco/complicaciones , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/tratamiento farmacológico , Amiodarona/administración & dosificación , Aspirina/administración & dosificación , Atropina/administración & dosificación , Ecocardiografía , Electrocardiografía , Epinefrina/administración & dosificación , Mutación/genética

Asunto(s)

Mujeres Trabajadoras/legislación & jurisprudencia , Mujeres Trabajadoras/psicología , Mujeres Trabajadoras/estadística & datos numéricos , Trabajo/historia , Trabajo/legislación & jurisprudencia , Economía/estadística & datos numéricos , Paraguay

RESUMEN

Contenido:Introduccion Cap.1 Generalidades Cap.2 Consideraciones teoricas de las caracteristicas de reservorios obtenidos a partir de los datos del DST.Permeabilidad.Daño a la formacion.Presion maxima del reservorio.Agotamiento.Radio de investigacion.Indicaciones de barrera Cap.3 Herramientas y tecnicas modernas utilizadas en DST.Resumen.Ensayos en pozo abierto.Ensayos en pozo entubado.Ensayos en pozos de gran volumen Cap.4 Hidraulica del DST Cap.5 Planificacion de la prueba de formacion.Definicion de la prueba.Preparacion del pozo.Preparacion del equipo.Uso de colchon.Programacion de la prueba Cap.6 Interpretacion cualitativa de una grafica de presion.Grafica tipica de una prueba de formacion con doble apertura y doble cierre.Interpretacion Cap.7 Analisis cuantitativo de la prueba de formacion.Teoria.Evaluacion-Metodo Horner.Metodo curvas Matching-Mc Kinley.Uso de un nuevo grupo de curvas tipo en el analisis de ensayos DST Cap.8 Aplicacion practica del analisis cuantitativo "Evaluacion de la prueba de formacion y produccion DST-FAF No.4 del pozo BJO-X44" (Campo Bermejo.Distrito Sur de Y.P.F.B.).Antecedentes.Desarrollo de la prueba.Interpretacion y evaluacion del ensayo Cap.9 Consideraciones economicas.Introduccion.Costos Cap.10 Conclusiones y recomendaciones.