SKELETAL DYSPLASIA DUE TO CONGENITAL DISORDERS OF GLYCOSYLATION

EG MARTINEZ DOMENECH; MA DELGADO; P SARRIÓN; G MATTHIJS; N GUELBERT; R DODELSON DE KREMER; S BALCELLS; D GRINBERG; CARLA G ASTEGGIANO

Barcelona

Congreso; 12th International Congress of Inborn Errors of Metabolism; 2013

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

Defects in N-, O-glycosylation and combined glycosylation pathways have been identified as Congenital Disorders of Glycosylation (CDG). Most of them are autosomal recessive, but multiple osteochondromatosis (EXT1/EXT2-CDG) was described as a dominant disease restricted to the cartilage. A peculiar skeletal phenotype has been described in CDG patients and it has gained special relevance over the past few years. In patients exposed to the cell hypoglycosylation due to altered glycosylation pathway, numerous extracellular matrix proteins undergo glycosylation defects that lead to skeletal manifestations. The aim of this work is to communicate the first CDG research program in Argentina to study the glycobiology in skeletal dysplasia associated with CDG. Here we report the results of (i) a cohort of 42 patients diagnosed with clinical osteochondromatosis, most of them presenting a severe phenotype (83%), including condrosarcoma (11%), with mutations detected in EXT1 (72%) or EXT2 (28%), (ii) a patient with osteopetrosis-like phenotype, transferring-IEF type-II and altered fucosylation observed by mass-spectrometry, in which only a heterozygous variation was found in COG6, p.V631M (c.1891G>A); and (iii) the screening for: GALNT3-CDG (hyperfosfatemic-tumoral calcinosis); LFNG-CDG (spondylocostal-dysostosis); SLC35D1-CDG (Schneckenbecken-dysplasia); and B4GALT7-CDG (Progeroid-variant Ehlers-Danlos). Our results highlight the hypoglycosylation effect on the genesis of skeletal manifestation in CDG. FONCyT-PICT2010/2824-UCC2012-SAF2011-25431-PIB2010AR-00473asteggianocarla@hotmail.com