Descripción clínica de pacientes pediátricos con enfermedades neuromusculares en una muestra de población chilena / Clinical description of pediatric patients with neuromuscular diseases in a Chilean population sample

OBJETIVO: Describir clínica y diagnóstico de 152 pacientes pediátricos asistentes al policlínico del Programa de Enfermedades Neuromusculares (ENM) en un centro terciario de la Región Metropolitana, Chile. METODOLOGÍA: Revisión de fichas programa EMN (2012-2016). RESULTADOS: 49% niñas, mediana de edad: 9 años (rango, 0­18), consultan por alteraciones de la marcha, debilidad e hipotonía. Segmentos más afectados son músculo y nervio periférico (92%). Diagnósticos más frecuentes son neuropatías adquiridas (26,1%), distrofias musculares (14,8%) y trastornos miotónicos (12,7%). Comorbilidades más frecuentes son patología traumatológica (23,2%) y discapacidad intelectual (13,4%). Los pacientes con patología hereditaria tienen mayor chance de requerir ventilación mecánica (OR 15,4; IC 95% 1,9­119,2) y presentar morbilidad traumatológica (OR 4,1; IC 1,03­16,4) que los con patología adquiridas. Confirmación genético-molecular en 38,4% de los pacientes con patología hereditaria. CONCLUSIONES: El conocimiento de características clínicas y posibilidades de estudio de las ENM puede mejorar las estrategias de atención.

INTRODUCTION: Neuromuscular diseases (NMS) represent a heterogeneous group of acquired and hereditary pathologies that affect the motor unit. There are few descriptive studies of patients with NMS in Chile and Latin America. OBJECTIVES: To clinically and epidemiologically characterize the pediatric population attending a polyclinic run using the NMS program of a hospital in the Metropolitan Region in Chile. Methodology: A review was made of database and clinical records of patients diagnosed with NMS between January 2012 and December 2016. RESULTS: A total of 142 patients, 51% of whom were male, with a median age 9 years (0-18 years), were included. The most frequent reasons for consultation were altered gait, decreased strength, and hypotonia. The most frequently affected segments were muscles and peripheral nerves (92% of the sample). The most frequent diagnoses were acquired neuropathies (26.1%), muscular dystrophies (14.8%), and myotonic disorders (12.7%). The most frequent comorbidities were traumatological pathologies (23.2%) and intellectual disabilities (13.4%). When comparing NMS with hereditary vs. acquired etiologies, those with hereditary etiologies had a higher risk of requiring mechanical ventilation (OR 15.4 [95%CI 1.9-119.2]) and having a traumatological disease (OR 4.1 [CI 1.03-16.4]) compared to those with acquired etiologies. For 38.4% of patients with hereditary etiologies, confirmation was obtained through molecular genetic testing. CONCLUSIONS: This study provides information on the frequency of NMS and their main comorbidities in a Chilean pediatric sample. These results provide information regarding current possibilities for studies and could aid in planning care for these patients in our country. Keywords: Neuromuscular disease, Muscular disease, Neuropathies, Neurological Diagnostic.

Descripción clínica de pacientes pediátricos con Enfermedades Neuromusculares en una muestra de población chilena / Neuromuscular Disease: Clinical and Epidemiological Characterization of a Chilean Pediatric Population

Las Enfermedades Neuromusculares (ENM) representan un grupo heterogéneo de patologías adquiridas y hereditarias que afectan la unidad motora. Existen escasos estudios descriptivos en Chile y Latinoamérica de pacientes con ENM. Objetivo: Caracterizar clínica y epidemiológicamente a población pediátrica asistente a policlínico del Programa de ENM en periodo de 3 años en hospital de Región Metropolitana. Pacientes y Método: Revisión de base de datos y fichas clínicas de pacientes con diagnóstico de ENM entre enero 2012 y diciembre 2016. Resultados: 142 pacientes, 51% sexo masculino, mediana de edad 9 años (0-18). Motivos de consulta frecuentes fueron alteración de la marcha, falta de fuerza e hipotonía. Los segmentos más afectados fueron músculo y nervio periférico (92% de la muestra). Los diagnósticos más frecuentes fueron Neuropatías Adquiridas (26,1%), Distrofias Musculares (14,8%) y Trastornos Miotónicos (12,7%). Las comorbilidades más frecuentes fueron las patologías traumatológicas (23,2%) y discapacidad intelectual (13.4%). Los pacientes con patología hereditaria presentaron mayor riesgo de requerimiento de ventilación mecánica (OR 15,4 [IC 95% 1.9-119.2]) y comorbilidad traumatológica (OR 4,1[IC 1.0316.4]) que los con patología adquiridas. 38,4 % de los pacientes con etiología hereditaria tuvieron confirmación genético-molecular. Conclusiones: Este estudio da información de la frecuencia de las distintas ENM y sus principales comorbilidades en una muestra pediátrica chilena. Aporta datos referentes a las posibilidades de estudio disponible en nuestro país y podría ser de ayuda en la planificación de la atención de estos pacientes. Palabras claves: enfermedad neuromuscular, enfermedad muscular, neuropatías, diagnóstico neurológico.

Neuromuscular diseases (NMS) represent a heterogeneous group of acquired and hereditary pathologies that affect the motor unit. There are few descriptive studies of patients with NMS in Chile and Latin America. Objective: To clinically and epidemiologically characterize the pediatric population attending a NMS polyclinic of a hospital in the Metropolitan region. Methodology: A database and clinical record review of patients diagnosed with NMS between January 2012 and December 2016 was performed. Results: A total of 142 patients, 51% of whom were male, with a median age 9 years (0-18 years), were included. The most frequent reasons for consultation were altered gait, lack of strength, and hypotonia. The most frequently affected segments were muscles and peripheral nerves (92% of the sample). The most frequent diagnoses were acquired neuropathies (26.1%), muscular dystrophies (14.8%), and myotonic disorders (12.7%). The most frequent comorbidities were traumatological pathologies (23.2%), and intellectual disabilities (13.4%). When comparing NMS with hereditary vs. acquired etiologies, those with hereditary etiologies had a higher risk of requiring mechanical ventilation (OR 15.4 [95%CI 1.9-119.2]) and having traumatological disease (OR 4.1 [CI 1.03-16.4]), compared to those with acquired etiologies. For 38.4% of patients with hereditary etiologies, confirmation was obtained through a molecular genetic test. Conclusions: This study provides information on the frequency of NMS and their main comorbidities in a Chilean pediatric sample. These results provide information regarding current possibilities for studies and could aid in planning care for these patients in our country. Palabras claves: Neuromuscular disease, Muscular disease, Neuropathies, Neurological Diagnostic.

High creatine kinase levels and white matter changes: clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency.

Primary deficiency of laminin alpha-2 due to mutations in the LAMA2 gene accounts for 30% of all patients with congenital muscular dystrophy. Here, we present seven patients with partial or total laminin alpha-2 deficiency (MDC1A) with a wide clinical spectrum, ranging from ambulant patients to patients who were never able to stand or sit. We identified two pathogenic mutations in the LAMA2 gene in all patients except for one patient in whom only one mutation was found. Six of the mutations were previously undescribed. In some of the milder cases, laminin alpha-2 expression in the muscle biopsy was only slightly reduced. These findings emphasize that analysis of the LAMA2 gene might be necessary in patients with muscle weakness, cerebral white matter changes and high creatine kinase levels, even in the presence of laminin alpha-2 in the muscle biopsy.

Aumento de transaminasas: una manifestación de distrofia muscular de Duchenne / Transaminases increase: a manifestation of Duchenne's muscular dystrophy

Commonly used in clinical practice, glutamic oxalacetic (GOT) and glutamic piruvic (GPT) transaminases are produced in various body tissues, including striated muscle, so their blood elevation is not due exclusively to liver disease. The objective of this study is to demonstrate the correlation between elevated creatinkinase (CK) and transaminases in patients with diagnosis of Duchenne muscular dystrophy (DMD), the most frequent neuromuscular disease in children. Patients and Method: Assessment in 61 children with diagnosis of DMD of CK, AST and ALT levels, and their correlation. Results: Aill patients had increase of CK ( = 13.363 IU/L), AST ( = 203 lU/L) and ALT ( = 194 IU/L) above normal values. The increase of transaminases related directly with the increase of CK. Conclusion: Patients with DMD have increased transaminases, so it is necessary to include this diagnostic possibility in a child with hypertransaminemia, prior to performing liver biopsy.

Las transaminasas que comúnmente se utilizan en clínica, glutámico oxalacética (GOT) y glutámico pirúvica (GPT) son producidas en varios tejidos del organismo entre los cuales se cuenta el músculo estriado, por lo que la elevación de transaminasas en sangre no es producida exclusivamente por enfermedades hepáticas. Objetivo: Demostrar la correlación entre el alza de la creatinkinasa (CK) y transaminasas en pacientes con el diagnóstico de distrofia muscular de Duchenne (DMD), la enfermedad neuromuscular más frecuente en niños. Pacientes y Método: Evaluación en 61 niños con diagnóstico de DMD de los niveles de CK, GOT y GPT y la relación entre ellos. Resultados: Todos los pacientes presentaron aumento de CK ( = 13.363 IU/L), GOT ( = 203 IU/L) y GPT ( = 194 IU/L) sobre los valores normales. El aumento de transaminasas se relacionó en forma directa con aumento de CK. Conclusiones: Los pacientes con DMD presentan transaminasas aumentadas, por lo que es necesario incluir esta posibilidad diagnóstica en niños con hipertransaminasemia, previo a realizar biopsia hepática.