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

M. B. BISTUÉ MILLÓN; M. A. DELGADO; N. B. AZAR; M.; N. GUELBERT; L. STURIALE; G. MATTHIJS; J. JAEKEN; C. G. ASTEGGIANO.

San Diego, USA

Congreso; 11th International Congress of Inborn Errors of Metabolism, San Diego August 29th – September, 2009, USA; 2009

ICIEM

Congenital Disorders of Glycosylation (CDG) are a rapidly growing family of diseases caused by defects in the biosynthesis of glycans attached to proteins and lipids. They have mostly a multisystem presentation, and have to be differentiated from protein variants and secondary CDG such as untreated classic galactosemia. Aim: To report the clinical, biochemical and molecular aspects of two siblings with unexplained CDG, in the context of the first CDG program in Argentina. Case report: We present two siblings born as the first and the third children of healthy Argentinean parents. One of them (a girl) had an early death (at the age of 4 months) and the other is now a 10 y-old girl. She showed liver dysfunction in the neonatal period, and has psychomotor retardation, hypotonia, microcephaly, seizures, feedings difficulties and hepatomegaly. She also developed strabismus and cataract.Methods: A) Analysis of serum N-glycoproteins using different assays: (1) Western blot (Wb), isoelectric focusing (IEF) and high performance liquid chromatography of transferrin (HPLC-Tf); (2) Enzymatic analysis of phosphomannomutase and phosphomannose isomerase activities in leucocytes; B) Lipid-linked oligosaccharide (LLO) analysis in fibroblasts, and D) Mass spectrometry (MS). Results: CDG-I was diagnosed based on the type 1 pattern of serum transferrin isoforms. CDG-Ia and CDG-Ib were excluded by enzymatic analysis. Secondary protein variants (polymorphisms) and other pathologies (galactosemia, fructosemia and alcohol abuse), were also excluded. LLO analysis showed no abnormal accumulation of intermediate precursors of the known forms of CDG-I. CDG-Ij and CDG-Ik were excluded by molecular analysis of ALG7 and ALG1 genes respectively. Discussion: We describe two siblings with a severe form of CDG-Ix. Studies are in progress to identify their basic defect. This CDG program allowed us to start a new genetic and metabolic chapter in our country and Latin America. Funded by: CONICET / FONCyT/ UCC.