Congreso Latinoamericano De Glicobiología
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NH 2 Asn COOH o Congreso hLys Ser Ser NH 2 COOH Latinoamericano de 5 Glicobiología Sociedad Latinoamericana de Glicobiología A.C. 2 - 4 Octubre 2019 CDMX Reunión 2a Biosíntesis, función y aplicación de los carbohidratos/glicanos en la salud Evento responsable con apropiación social de la ciencia. SPONSORS ORGANIZING COMMITTEE Carla Asteggiano, PhD. Edgar Zenteno Galindo, MD, PhD. Héctor Mora Montes, PhD. Iván Martínez Duncker, MD, ScD. Roberta Salinas Marín, PhD. Tonatiuh Ramírez Reivich, PhD. Verónica Vallejo Ruiz, PhD. SUPPORT TO THE ORGANIZING COMMITTEE AND TECHNICAL EDITION Sandra R.Manrique Hernández, BSc. The realization of this event was possible thanks to the financial support received from the National Science and Technology Council (CONACYT- México) through the grant 2019 of the Program for Scientific, Technological and Innovation Activities, project 299387 and to our sponsors. Congenital Disorders of Glycosylation: Expect the Unexpected. Hudson H. Freeze1, Zhijie Xia1, Paulina Sosicka1 Bobby Ng1 and Carlos R. Ferreira2. 1Sanford Burnham Prebys Medical Discovery Institute, La Jolla CA, USA. 2National Human Genome Research Institute, National Institutes of Health, Bethesda MD, USA. [email protected] The Congenital Disorders of Glycosylation (CDG) comprise ~140 genetic disorders that affect biosynthesis, recognition and function of glycans. One series of CDGs is caused by recessive bi- allelic mutations in 7 of the 8 members of the Conserved Oligomeric Golgi (COG) complex, which maintains ER-Golgi homeostasis. Mutations cause improper glycosylation because they disrupt normal Golgi organization and trafficking. Patients typically have hypotonia, developmental delay, intellectual disability, variable skeletal problems and dysmorphology. Many die early. Our first surprise: We identified 14 patients with a characteristic skeletal abnormality and progeroid dwarfism, but normal intellectual development. All patients have the identical de novo, dominant mutation in only a single allele of COG4. This generates an abnormally small Golgi and changes trafficking, but it has negligible effects on glycosylation in cells or patients. However, various collagens accumulate within the ER, leaving a collagen-depleted extracellular matrix. The mutant protein accumulates due to slower turnover which alters normal COG4 interactions with a plethora of cytoplasmic proteins. Our goal is to determine how this single mutation produces these cellular abnormalities and profound clinical presentations. Our second surprise: We discovered severely disabled patients with mutations in fucose kinase that activates diet-derived or salvaged fucose for glycosylation. That pathway was considered insignificant, contributing <10% to fucosylation. Instead, the de novo pathway from GDP- Mannose is known as the major contributor. We found that very low concentrations (0.5-20 M) of exogenous fucose progressively inhibit the de novo pathway, completely by ~50 M. Surprisingly, GDP-Fucose derived from Glc is much more sensitive to this inhibition, than that derived from Man. Cells seem to distinguish multiple pools of GDP-Fuc based on their origin. At low concentrations, the glucose transporter (GLUT1) delivers fucose, but at higher ones amiloride-sensitive micropinocytosis is the major contributor. Labeling of multiple cells lines with 13C- fucose shows that different glycans can selectively choose de novo or salvaged fucose. The cell knows about different pools, but it is not clear how it knows this. What is clear is that paying attention to patients with rare diseases can enrich and enlighten our basic science. Study of expression of specific glycans on platelet membrane in congenital disorders of glycosylation patients. Papazoglu G.M.1,2, Salinas R.3, Pereyra M.I.4, Cubilla M.1,2, Martinez –Duncker I.3, Asteggiano C.G. 1,2,5. 1Centro de Estudio de las Metabolopatías Congéntias (CEMECO), Hospital de Niños de la Sma. Trinidad. Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Ferroviarios 1250, Córdoba (CP: 5014), Argentina. 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. 3Cell Dynamics Research Center, Human Glycobiology and Molecular Diagnosis Laboratory, Morelos State Autonomous University, Mexico. 4Servicio de Inmunología. Hospital de Niños de Sma. Trinidad, Córdoba, Argentina. 5Facultad de Medicina, Universidad Católica de Córdoba, Córdoba-Argentina. [email protected] Introduction: Congenital Disorders of Glycosylation (CDG) are human genetic diseases due to defects in the pathway of glycoconjugates. Most of these patients present thrombo-hemorragic events. Objective: To contribute to the knowledge of the physiopathological bases associated with thrombo-hemorrhagic alterations in CDG patients. Methodology: The expression of total glycans in platelet membrane we studied in a PRP population of normal controls (6) and PRP from a PMM2-CDG. The platelet population (PRP) was identified by flow cytometry labeling using the anti CD-41-PE antibody. A panel of 10 biotinylated lectins labeled with Stretavidin and conjugated with an Alexa-647 antibody were tested to detect glycans. We compared the value of MFI observed in the control group for each lectin studied in relation to the values obtained in the patient PMM2-CDG, by means of a Student's T test considering a significant difference the lower values p = <0.05. Results: The MFI values showed no significant differences between the controls and the patient with PMM2-CDG in the following readings: AAL, CON-A, UEA-I, RCA-I, MAA-I, WGA. In addition, we were able to corroborate that expression of PNA, GSL-I and GSL-II lectins was not observed, indicating very low levels of O-glycans in the platelet membrane proteins. However, this study showed significant differences (p <0.05) in the expression of the SNA lectin between the controls and the patient. Conclusion: For the first time we have characterized the profile of glycans present in platelets of a PMM2-CDG patient, observing a decrease in the expression of SNA lectin (p <0.05), consequently, a lower Sialic Acid content. The decrease in the expression of Sialic acid could increase the platelet clearence, (thrombocytopenia) and as a result, a potential risk of hemorrhage in these patients. We observed that the platelet proteins are mainly N-glycosylated. CONICET, FONCyT, UCC. Mucopolysaccharidosis: The clinical experience in the northeast of Mexico. Luz María Sánchez Sánchez. Pediatrician and Neonatologist. Hospital de Especialidades UMAE 25, IMSS, Monterrey, N.L. [email protected] Mucopolysaccharidoses (MPS) are a group of clinically heterogeneous diseases due to the deficiency of lysosomal enzymes required for the breakdown of mucopolysaccharides or glycosaminoglycans (GAGs). The storage products cause progressive damage of cells, tissues, and organ systems, leading to a wide range of clinical manifestations and early death. There are 7 types of MPS, with 11 enzyme deficiencies. Each of them shares some clinical features like joint and skeletal dysplasia, coarse facial features, corneal clouding, inguinal or abdominal hernias, recurrent upper respiratory tract infections, heart valve disease, carpal tunnel syndrome, and variable neurological involvement. Each one has severe and attenuated phenotypes, so the clinical diagnosis is not as easy as it may seem. Enzyme replacement therapy is available in Mexico for MPS I, II, IV and VI. A good number of patients have received this treatment in some medical institutions in the country, with different results because of the heterogeneity of the disease, even within the same type of MPS. There are still many challenges in the diagnosis and treatment of MPS. I will present our clinical experience with MPS in the last 13 years in the Northeast of Mexico: the clinical features and phenotypes, the genotypes, the journey to diagnosis, the challenges, the response to treatment, the outcome, and the lessons that we have learned. Application of genomic technologies in genetic diagnosis. Carmen Alaez Verson. Laboratorio de Diagnóstico Genómico (LDG), Instituto Nacional de Medicina Genómica (INMEGEN), Periférico Sur 4809, México City, México. [email protected] The completion of the Human Genome Project in 2003 was the beginning of genomic medicine era, in which information from genomes would guide clinical decision and contribute to the achievement of personalized medicine. Personalized medicine also requires the availability of appropriate genetic diagnosis for individual patients. With the use of next-generation sequencing (NGS) technology, identification of genetic variations related to disease causality is progressing very fast. Big efforts are being performed for understanding the rare monogenic and complex traits and revealing the genetic basis of the disease based on exome sequencing. These efforts are improving diagnosis, increasing the knowledge about the mechanism of disease and genotype-phenotype correlation, helping to new drugs development, and disease management either by available treatments or genetic counseling. The application of NGS to clinical diagnosis has different scales depending on the size of the targeted region and the application purpose. Complexity and cost increase from the analysis of a single large gene to a group of genes (panel), to the whole exome (1–2% of the genome, ~20,000 genes). The genes included in a panel are selected based on a common pathway, a defined phenotype, shared or similar phenotypes, or known complex disorders.