Congenital Disorders of Glycosylatione (CDG): the Italian experience in the Euroglycanet network (2005-2010)
Written by R. Barone, L. Sturiale, D. Garozzo, G. Sorge, A. Fiumara Policlinico - Università di Catania; - Istituto di Chimica e Tecnologia dei Polimeri - CNR – Catania., published 3 months ago.
Congenital Disorders of Glycosylation (CDG) are inherited metabolic diseases due to defective synthesis of glycoproteins and other glycoconjugates. Almost 25 different diseases have been identified along the N-glycosylation pathway.
CDG are characterized by global developmental delay of variable degree and possible occurrence of central nervous system malformation, mainly cerebellar atrophy. Also, dysmorphic features, acquired microcephaly, sensorial defects, epilepsy, peripheral neuropathy and multisystem signs may occur.
Euroglycanet is an European network focused to enhance CDG diagnosis and characterization and to enhance CDG knowledge among professionals.
Over the last five years (2005-2010), at the Referral Centre for inherited metabolic diseases – University of Catania, Italy we analysed almost 3000 serum samples for CDG by the transferrin IEF analyses.
Serum samples with abnormal transferrin IEF profiles underwent ad hoc MALDI-TOF glycosylation analyses developed at the mass spectrometry centre of the ICPT-CNR Catania-Italy. As a further step, pathological samples entered the Euroglycan laboratory network for enzyme and molecular analyses.
We identified 21 patients with molecular defects along the N-glycosylation pathway.
Fourteen patients had PMM2-CDG (CDG-Ia), that is the most common among CDG subtypes. In addition to the classic, severe PMM2-CDG, we could detect a “mild” phenotype based on the developmental pattern, absence of microcephaly, and mild cerebellar atrophy. All patients with “mild” PMM2-CDG were compound heterozygous for p.L32R mutation of the PMM2 gene.
Seven patients (38%) had no PMM2-CDG. They showed dysmorphic features (7/7), microcephaly (6/7), severe psychomotor delay (6/7), drug-resistant epilepsy with onset in the first year of life, (6/7), visual impairment (5/7). They had no cerebellar atrophy.
Based on our work we suggest that CDG should be considered among inherited metabolic diseases with early onset epileptic encephalopathy.
References
Barone R, Sturiale L, Fiumara A, Uziel G, Garozzo D, Jaeken J. Borderline mental development in a congenital disorder of glycosylation (CDG) type Ia patient with multisystemic involvement (intermediate phenotype).J Inherit Metab Dis. 2007 Feb;30(1):107.
Barone R, Sturiale L, Sofia V, Ignoto A, Fiumara A, Sorge G, Garozzo D, Zappia M.Clinical phenotype correlates to glycoprotein phenotype in a sib pair with CDG-Ia.Am J Med Genet A. 2008 Aug 15;146A(16):2103-8.
Barone R, Sturiale L, Garozzo D.Mass spectrometry in the characterization of human genetic N-glycosylation defects.Mass Spectrom Rev. 2009 May-Jun;28(3):517-42.
Written by R. Barone, L. Sturiale, D. Garozzo, G. Sorge, A. Fiumara Policlinico - Università di Catania; - Istituto di Chimica e Tecnologia dei Polimeri - CNR – Catania., published 3 months ago.
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