Molecular Characterization of the GBA Gene in Patients from Southwest of Colombia with Gaucher Disease

Abstract Introduction Gaucher's disease (GD) is an autosomal-recessive lysosomal storage disorder that results from hereditary deficiency of the acid glucocerebrosidase enzyme, encoded by the GBA gene necessary for the degradation of glucosylceramide. Objective molecularly characterize the variants found in the GBA gene present in patients from the Southwest of Colombia with GD. Material and methods 19 patients were included in the study, clinically and enzymatically diagnosed with GD. A molecular analysis of the GBA gene was performed and the variants were subsequently searched in different population and clinical databases. A bioinformatic analysis was performed. Results The variants in the GBA gene reported were classified into: 14/19 homozygous patients, 4/19 compound heterozygote and 1/19 heterozygous. The presence of 7 variants coding for 8 different genotypes was reported. Also the known mutations like Asn409Ser, p.Leu483Pro, p.Lys237Glu, p.Glu427Lys, and p.Arg535His were identified in these patients. The most frequent genotype was p. Asn409Ser / Asn409Ser (36%). All the variants presented a pathogenic clinical significance. Conclusion The given study will make it possible to understand the susceptibility to GD in the population. This can help maintain the health quotient of the population through premarital counseling and therefore minimize the burden of disease among the population.

Consenso del Grupo de Estudio Latinoamericano de Mieloma Múltiple (MM) GELAMM para el manejo del MM en estado de pandemia SARS-CoV-2 / COVID- 19 / Consensus of the Latin American Study Group on Multiple Myeloma (MM) GELAMM for the management of MM in a state of Pandemic SARS-CoV-2 / COVID-19

Resumen La enfermedad por COVID-19 fue detectada a finales de 2019 en Wuhan, China. Debido a su rápida propagación fue declarada emergencia sanitaria de forma inicial y luego de identificar casos fuera de China con transmisión autóctona y caracterizado por una mortalidad considerablemente alta en países como Italia y España, fue declarada pandemia por la Organización Mundial de la Salud. Se ha evidenciado que los pacientes mayores y con antecedentes de enfermedades crónicas incluido el cáncer desarrollan una enfermedad severa, presentando mayor riesgo de mortalidad por SARS-CoV2/ COVID-19. Lo anterior es por supuesto especialmente importante en el manejo de pacientes con Mieloma Múltiple (MM), generando en el personal Médico nuevos desafíos, oportunidades de mejora y aprendizajes, que aporten al análisis riesgo-beneficio del tratamiento inmunodepresor en este tipo de patologías. El consenso tiene como objetivo brindar orientación sobre el manejo de pacientes con MM en estos momentos donde el profesional de la salud requiere información para llevar a cabo terapias eficientes en el cuidado del paciente.

Abstract COVID-19 disease was detected in late 2019 in Wuhan, China. Due to its rapid spread, it was initially declared a health emergency, but after cases with indigenous transmission were identified outside China, characterized by considerably high mortality in countries such as Italy and Spain, it was declared a pandemic by the World Health Organization. It has been shown that elderly patients with a history of chronic diseases, including cancer, develop a severe disease, presenting a higher risk of mortality from SARS-CoV2 / COVID-19. This becomes especially important in the management of patients with Multiple Myeloma (MM), generating new challenges, opportunities for improvement and learning opportunities in the health professionals, which will contribute to the risk-benefit analysis of immunosuppressive treatment for this type of pathology. The consensus aims to provide guidance for the management of patients with MM in these times when the health professional requires information to deliver efficient therapies in patient care.

Recomendaciones para el cuidado de pacientes con cáncer y neoplasias hematológicas en el estado de pandemia COVID-19 en Colombia / Care recommendations for patients with cancer and hematological neoplasms amid the COVID-19 pandemic in Colombia

Resumen Ante la pandemia COVID 19, declarada en marzo de 2020 por la Organización Mundial de la Salud (OMS), desde la Asociación Colombiana de Hematología y Oncología (ACHO) hemos venido emitiendo comunicaciones destinadas a orientar a los profesionales de la salud implicados en el tratamiento de pacientes hematológicos y oncológicos. Consideramos importante realizar una nueva actualización dada la fase de mitigación de la pandemia que actualmente estamos enfrentando y ante el planteamiento gubernamental de desdescalonamiento progresivo, de la cuarentena. Estas recomendaciones no pretenden imponer una conducta única pues entendemos que cada caso es particular y debe actuarse individualizando a cada situación específica. Están basadas en documentos emitidos por asociaciones científicas oncológicas y hematológicas reconocidas y son susceptibles de sufrir modificaciones a medida que se disponga de mayor información.

Abstract In response to the Covid-19 pandemic, declared in March 2020 by the World Health Organization (WHO), the Colombian Association of Hematology and Oncology (ACHO) has been issuing communications aimed at providing guidance to health professionals involved in the treatment of hematological and oncological patients. Considering the pandemic mitigation phase we are currently facing, and the government's approach to progressively tapering-off the quarantine, we deem it important to release a new update. These recommendations are not intended to impose a single conduct, since we understand that each case has particular characteristics and therefore it must be acted upon by individualizing each specific situation. The recommendations are based on documents issued by well-known cancer and hematological scientific associations, and are subject to change as more information becomes available.

Variantes del gen GBA en el Suroccidente Colombiano / Variants of the GBA gene in the Southwest of Colombia

Introducción: La Enfermedad de Gaucher (EG) es un trastorno genético autosómico recesivo, causado por la deficiencia de la enzima B-Glucocerebrosidasa acida (GBA). En Colombia se ha estimado una prevalencia de 1:266.441 habitantes. Sin embargo, el país no cuenta con datos exactos sobre la incidencia, prevalencia y carga poblacional de esta enfermedad. Objetivo: Con el objetivo de caracterizar molecularmente las variantes encontradas en el gen GBA presentes en pacientes del Suroccidente Colombiano con enfermedad de Gaucher. Materiales y métodos: Se incluyeron 19 pacientes en el estudio, 57,8% de género masculino, con intérvalo de edad entre 4 y 71 años, diagnosticados clínica y enzimáticamente con EG. Se realizó un análisis molecular del gen GBA y posteriormente se buscaron las variantes en diferentes bases de datos poblacionales y clínicas; además se realizó análisis bioinformático para evaluar el posible impacto de las variantes de interés en la estructura y funcionalidad de la proteína. Resultados: Se encontraron 14/19 pacientes homocigotos; 4/19 heterocigotos compuestos y 1/19 heterocigotos). Se reportó la presencia de 7 variantes que codifican para 8 genotipos diferentes. El genotipo más frecuente es p.Asn409Ser/p.Asn409Ser (36%). De las 7 variantes encontradas, se reportó que específicamente p. Asn409Ser (10/23 alelos) y p.Leu483Pro (3/23 alelos) y p.Lys237Glu (3/23 alelos), están presentes en el 69,5% de los alelos. Todas las variantes presentaron una significancia clínica patogénica. Conclusiones: Este trabajo contribuye al establecimiento de las bases moleculares de la EG en los pacientes del Suroccidente Colombiano, permitiendo realizar una correlación genotipo-endotipo-fenotipo. Así mismo, se determina que los algoritmos de diagnóstico que incluyen análisis molecular y herramientas predictivas bioinformáticas permiten mejorar el diagnóstico, el tratamiento y el pronóstico de los pacientes afectados por EG, generando un impacto positivo en el seguimiento de los afectados, de la mano de una correcta consejería genética y estudios de portadores.

Introduction:Gaucher's disease (EG) is an autosomal recessive genetic disorder, caused by a deficiency of the acid B-Glucocerebrosidase (GBA) enzyme. In Colombia, a prevalence of 1: 266.441 inhabitants have been estimated. However, the country does not have exact data on the incidence, prevalence and population burden of this disease. Objective: molecularly characterize the variants found in the GBA gene present in patients from the Southwest of Colombia with Gaucher disease. Material and methods: 19 patients were included in the study, 57,8% male, with an age range between 4 and 71 years, clinically and enzymatically diagnosed with GD. A molecular analysis of the GBA gene was performed and the variants were subsequently searched in different population and clinical databases; In addition, a bioinformatic analysis was performed to evaluate the possible impact of the variants of interest on the structure and functionality of the protein. Results: 14/19 homozygous patients were found; 4/19 compound heterozygotes and 1/19 heterozygotes). The presence of 7 variants coding for 8 different genotypes was reported. The most frequent genotype was p.Asn409Ser/p.Asn409Ser (36%). Of the 7 variants found, it was reported that specifically p. Asn409Ser (10/23 alleles) and p.Leu483Pro (3/23 alleles) and p.Lys237Glu (3/23 alleles), are present in 69,5% of the alleles. All the variants presented a pathogenic clinical significance. Conclusion: This work contributes to the establishment of the molecular bases of GD in patients from the Southwest of Colombia, allowing a genotype-endotype-phenotype correlation to be carried out. Likewise, it is determined that diagnostic algorithms that include molecular analysis and bioinformatic predictive tools allow improving the diagnosis, treatment and prognosis of patients affected by GD, generating a positive impact on the follow-up of those affected, hand in hand with correct genetic counseling and carrier studies.