A BROAD SPECTRUM OF CONGENITAL DISORDER OF GLYCOSYLATION SUBTYPES IN ARGENTINA

ASTEGGIANO; MB BISTUÉ MILLÓN; MA DELGADO; P SARRIÓN; G MARTÍNEZ DOMENECH; N GUELBERT; S BALCELLS; D GRINBERG; R DODELSON DE KREMER.

Birmingham

Congreso; Annual Symposium of the Society for the Study of inborn errors of Metabolism; 2012

Society for the Study of Inborn Errors of Metabolism (SSIEM)

CDG are due to defects in N-, O-glycoproteins and glycolipids. Their spectrum ranges from multisystem to mono-organ disease. Most CDG are autosomal recessive, except multiple osteochondromatosis (EXT1/EXT2-CDG), characterized by the formation of multiple cartilage-capped tumors. Two glycosyltransferases involved in heparan sulphate elongation have been identified. The aim is to increase the knowledge on human glycobiology in a broad spectrum of CDG in Argentina. Using transferrin isoelectric-focusing, mass spectrometry and lipid-Linked-Oligosaccharides, we identified six patients with abnormal N-glycosylation. Studies are in progress to elucidate the defect. The initial work-up has been completed in P1 and the exome was sequenced in collaboration with Prof. Gert Matthijs. P1 has two mutations in GALT gene, despite normal galactose levels. Regarding EXT1/EXT2-CDG, DNA was studied by genotyping and MLPA. Twenty Latin-American patients had a severe phenotype and two patient presented malignant transformation to chondrosarcoma. We have found the molecular bases of 85% patients, 65% in EXT1 and 20% in EXT2. By MLPA we found two complete deletions in EXT1 and in EXT2 gene. This interdisciplinary research program in Argentina is the beginning of a "CDGnet Latin America? to promote scientific research, diagnosis and specific management of patients with Congenital Disorders of Glycosylation