Genotype and Phenotype Characterization of Patients with Mucopolysaccharidosis IV-A in Chile.

Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children's Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases. Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.

[Cytogenetic and molecular profile of genetic diseases in Puerto Montt main hospital]. / Caracterización citogenético-molecular de enfermedades genéticas en el Hospital Base de Puerto Montt.

BACKGROUND: Chromosome aberrations (CA) are the main etiology of multiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of moderate and severe degree. They account for 0.3 to 1% of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. AIM: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. PATIENTS AND METHODS: One hundred and eighty patients, 27 with a clinical diagnosis of Down syndrome, derived for the suspicion of a genetic disease, were studied. A karyogram was performed in all of them and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) were carried out. RESULTS: Among the 153 patients without Down syndrome, 20 (13%) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25% respectively) and four had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 of the 30 patients in whom these were requested. CONCLUSIONS: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.

Impacto de un entrenamiento de simulación virtual remota sincrónica para el tratamiento inicial del accidente cerebrovascular isquémico en estudiantes de medicina / Impact of synchronous remote virtual simulation training, for the initial management of ischemic stroke in medical students

Introducción: El accidente cerebrovascular (ACV) es una patología prevalente y dependiente del tiempo. Su tratamiento completo inicial es competencia obligatoria del médico general en Chile. En el contexto de la enseñanza clínica tradicional, hay pocas oportunidades de práctica en ese momento de la evolución de los casos. El objetivo fue evaluar el efecto de un programa de simulación virtual remota sincrónica para el tratamiento inicial del ACV en estudiantes de quinto año de medicina.Sujetos y métodos.Estudio cuantitativo, cuasi experimental. Se realizaron cinco sesiones, en días separados, en grupos de tres estudiantes. Cada sesión consistió en tres escenarios de simulación virtual de complejidad creciente, administrada de manera remota, con registro de desempeño individual y debriefing grupal. Se calculó la confiabilidad y se utilizó la prueba de Wilcoxon para muestras relacionadas con p < 0,05 como estadísticamente significativa para comparar los cuestionarios pre- y poscurso.Resultados.Se observó una mejoría del diagnóstico y el tratamiento farmacológico inicial del ACV entre el primer y el tercer casos. Los participantes declararon que la experiencia con el simulador creó oportunidades para la práctica clínica simulada y promovió el desarrollo de la formación en comunicación (p < 0,005). La satisfacción con el programa medida después del término del curso mostró un alto grado de acuerdo promedio.Conclusiones.La simulación virtual aplicada en un programa de práctica deliberada, con debriefing guiado por un instructor, mejoró las competencias para el tratamiento inicial del ACV en estudiantes de grado de medicina y fue muy bien valorada por los estudiantes. (AU)

Introduction: Stroke is a prevalent and time-dependent pathology. Its complete initial management is a mandatory competence of the general practitioner in Chile. In the context of traditional clinical teaching, there are few opportunities for practice at that moment of the evolution of cases. The objective was to evaluate the effect of a remote virtual simulation program, synchronous with debriefing, for the initial management of stroke in fifth year medical students.Subjects and methods.Quantitative, quasi-experimental study. Five sessions were conducted on separate days in groups of three students. Each session consisted of three virtual simulation scenarios of increasing complexity, administered remotely, with individual performance recording and group debriefing. Reliability was calculated and the Wilcoxon test for related samples with p < 0.05 was used as statistically significant to compare pre and post course questionnaires.Results.Improvement in the diagnosis and initial pharmacological management of stroke was observed between the first and third cases. Participants stated that the simulator experience created opportunities for simulated clinical practice and promoted the development of communication training (p < 0.005). Satisfaction with the program measured after completion of the course showed a high degree of average agreement.Conclusions.Virtual simulation applied in a deliberate practice program, with instructor-guided debriefing has improved competencies for the initial management of stroke in undergraduate medical students and was highly valued by the students. (AU)

Utility of rare disease registries in latin america.

There are many registries in Latin America as dialysis and kidney transplantation, breast cancer, primary immunodeficiency, acute coronary syndromes, but the focus here are the registries of lysosomal storage diseases (LSD) because is our experience. Registry of Gaucher disease, Fabry disease, Pompe disease, and mucopolysaccharidosis type I are comprehensive observational voluntary programs that aim to collect clinical and laboratory data of initiation, progression, and evolution of those diseases, with and without treatment, using questionnaires of quality of life and/or skills and functions. There are two more programs of LSD: Hunter outcome survey and Fabry outcome survey. The registries are a kind of phase IV clinical trials, postmarketing studies delineate additional information including the drug's risks, benefits, and optimal use, and in addition we have data from natural history. The demographics of the Gaucher, Fabry, MPS I, and Pompe Registries show that a total of patients, being 16%, 8%, 15%, and 7%, respectively, of this population, and 19%, 19%, 18%, and 13%, respectively, of all physicians participating in the program are from Latin America. In the Gaucher Registry, we can observe that the percentage of children in Latin America (29%) is bigger than the rest of the world (20%), what can mean more severe disease in this population. These diseases are rare, and a database of clinical data from a larger number of patients gives us the opportunity to know about the natural history of these diseases, their phenotypic variability, and the response to specific enzyme replacement therapy in our population.

Caracterización citogenético-molecular de enfermedades genéticas en el Hospital Base de Puerto Montt / Cytogenetic and molecular profile of genetic diseases in Puerto Montt main hospital

Background: Chromosome aberrations (CA) are the main etiology of múltiple congenital malformations, recurrent abortions and intellectual disability (ID) specifically of modérate and severe degree. They accountfor 0.3 to 1 percent of newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic deletions or duplications smaller than 10 MB that are overlooked by conventional cytogenetic studies. Aim: To report the results of cytogenetic and molecular studies performed in patients with a congenital malformation disease or ID with or without dysmorphic features, attended in a regional hospital. Patients and Methods: One hundred and eighty patients, 27 with a clinical diagnosis ofDown syndrome, derivedfor the sus-picion of a genetic disease, were studied. A karyogram was performed in all ofthem and in 30 cases additional molecular studies, such as fluorescence in situ hybridization (FISH) orpolymerase chain reaction (PCR) were carried out. Results: Amongthe 153 patients without Down syndrome, 20 (13 percent) had a genetic abnormality responsible for the altered phenotype. Sixteen had a chromosome aberration (structural and numerical aberrations in 75 and 25 percent respectively) andfour had genetic molecular alterations. Additional studies were performed to confirm or better characterize the chromosome aberration in 13 ofthe 30 patients in whom these were requested. Conclusions: Chromosome and specific genetic molecular studies in selected cases help to characterize patients with genetic diseases. The collaboration between academic and health care facilities is crucial.

Contaminación fecal y enteroparasitosis en el medio rural: un plan de extensión a cargo de alumnos universitarios / Fecal contamination and enteroparasites in rural communities: a plan implemented by university students

Durante el período 1985-1991, un equipo multidisciplinario de estudiantes universitarios diseñaron y llevaron a la práctica un plan, destinado a disminuir la contaminación fecal en comunidades rurales. La educación constituyó el principal instrumento utilizado de trabajo de este plan. Las acciones consistieron en un trabajo en terreno que incluyó una encuesta a la comunidad sobre condición socio-económicas, higiene, prevalencia y conocimientos sobre infecciones parasitarias transmitibles por vía fecal. Junto con la encuesta, se realizó un examen coproparasitario a los niños de 2 a 12 años y se organizan jornadas de motivación y educación a la comunidad. Además se capacitó a los profesores básicos de la comuna para que ellos sean los continuadores del plan a nivel local. Hasta ahora han sido visitados 21 sectores rurales y se han realizado 7 cursos para profesores. Los resultados del examen copro-parasitario indican que un 53,5% está infectada. Los protozoos patógenos más frecuentes fueron Giardia lamblia (17,5%) y Entamoeba histolytica (6,9%). Los vermes más corrientes fueron A. lumbricoides (5,5%) y Trichuris trichiura (5,4%). La magnitud de la tarea ha dificultado la evaluación de los aspectos educativos desde el punto de su eficacia en la erradicación de la contaminación fecal en el medio rural, sin embargo se ha diseñado un plan que, a partir de 1991, contempla continuar la acción en una sola localidad, lo que permitirá una adecuada evaluación de estos aspectos