CONGENITAL DISORDERS OF GLYCOSYLATION: First clinical, biochemical, enzymatic and molecular investigations in Argentina

ASTEGGIANO CG*1; BOHL L.1; DELGADO A1; AZAR NB1; OLLER DE RAMIREZ AM1; GUELBERT N1; MALAMUD H1; GHIO A1; BRIONES P.2; ARTUCH R3; VILASECA A.3; MATTHIJS G.4; JAEKEN J.5; DODELSON DE KREMER R1.

Paris, Oct 18-19

Congreso; The 3rd International Meeting on Congenital Disorders of Glycosylation and related disorders; 2007

Red Euroglycanet / Orphan Academy

Congenital Disorders of Glycosylation (CDG) are genetic, multisystem diseases, with mostly predominant cerebral involvement (such as psychomotor retardation, convulsions, axial hypotonia and cerebellar hypoplasia), associated with involvement of nearly any other organ depending on the CDG type (hepatopathy, coagulopathy, enteropathy, etc.) Objective: To develop and to standardize the theoretical and experimental bases of this rapidly growing chapter of clinical investigation in Argentina and Latin America, applying a protocol of investigation in both pediatric and adult patients with an unexplained clinical syndrome. Methodology: Serum transferrin and haptoglobin were studied in 500 pediatrics and adult patients by means of: a) western blot (Wb) and b) isoelectric focusing (IEF). Phosphomannomutase (PMM2) and phosphomannose isomerase (PMI) activities were measured in leucocytes. Results: Twenty abnormal patterns of Tf IEF were obtained: (1) cathodal shifts with a type 1 pattern (increased di-and/or asialotransferrin (n:2) or with a type 2 pattern (increased trisialotransferrin and/or other cathodal bands (n:6). Transferrin protein variant were excluded in this group. (2) Anodal shifts (n:12) due to transferrin protein variants. In the group with a type 1 pattern PMM2 and PMI deficiency were excluded. Discussion: The implementation of a protocol, the systematic search and the use of techniques of increasing specificity allowed to obtain the first results. In the patients with a type 1 pattern, the next step will be dolichol-linked oligosaccharides analysis in fibroblasts. The patients with a type 2 pattern will be further studied by glycan analysis of serum Tf or of total serum proteins. CONICET PIP(6338)/MINISTERIO DE SALUD (ARGENTINA).