“Clinical, biochemical and molecular studies of two CDG-Ix patients in the context of the first program for the Congenital Disorders of Glycosylation studies in Argentina”

BISTUÉ MILLÓN MB.; DELGADO MA; AZAR NB; GUELBERT N; DI RIENZO, M.; MATTHIJS G.; JAEKEN J.; DODELSON DE KREMER; ASTEGGIANO CG

Cancún, México

Congreso; VII Congreso Latinoamericano de Errores Innatos del Metabolismo y Pesquisa Neonatal; 2009

Sociedad Latinoamericana de Errores Innatos del Metabolismo y Pesquisa Neonatal.

Clinical, biochemical and molecular studies of two CDG-Ix patients in the context of the first program for the Congenital Disorders of Glycosylation studies in Argentina. Bistué Millón MB.(1); Delgado MA(1); Azar NB(1); Guelbert N(1); Di Rienzo, M.(1); Matthijs G.(3); Jaeken J.(3); Dodelson de Kremer(1); Asteggiano CG(1,2). (1) Centro de Estudio de las Metabolopatías Congénitas (CEMECO), Cs. Médicas, Univ. Nac.  Córdoba, Argentina, (2) Cát. Qca. Biológica, Fac. de Medicina, Univ. Católica de Córdoba, Argentina, (3) Department for Human Genetics/Center for Metabolic Diseases, Katholieke Universiteit Leuven, Belgium. Congenital Disorders of Glycosylation (CDG) is a constantly growing family of diseases caused by defects in N- or O-glycoproteins biosynthesis with a severe multisystemic presentation. A differential CDG diagnosis is necessary with secondary protein variants and other pathologies including untreated classic galactosemia. Aim: To report the clinical, biochemical and molecular aspects for CDG characterization of two siblings, in the context of the first program of these pathologies in Argentina. Methodology: A) Analysis of serum N-glycoprotein were performed using different assays: (1) Western Blot (WB), isoelectric focusing (IEF) and HPLC of transferrin (Tf); (2) Enzymatic activities for CDG Type Ia (phosphomannomutase) and Ib (phosphomannose isomerase) in leucocytes; B) Lipid linked oligosaccharides (LLOs) analysis in fibroblast, and D) Mass Spectrometry (MS) were performed. Results: CDG I diagnosis was made based on WB, IEF, HPLC and MS patterns of transferin isoforms. CDG-Ia and –Ib were excluded by specific enzyme analysis. Secondary protein variants and other pathologies were also excluded. LLO analysis shows no abnormal accumulation of any intermediate precursors associated with CDG-Ia-Il. We found out an increase in the levels of galatose (BL 25 ml/dl and BE 12,4 ml/dl), however, their  enzymatic activities remained normal.  Discussion: We describe two siblings with a severe form of CDG-Ix observed by different methodology. LLO analysis was not consistent with any of CDG-type I. One patient (BL) died and the other has a severe neurological deterioration. It is in progress a final diagnosis as a possible new type of CDG with an eventual galactose metabolism relation.  CONICET/FONCyT/UCC.