Clinical phenotype correlates to glycoprotein phenotype in a sib pair with CDG-Ia

Congenital disorder of glycosylation (CDG) type Ia (PMM2 mutations) is the most common genetic disorder of protein N-glycosylation. The wide clinical spectrum with mild to severe impairment of neurological function and extensive allelic heterogeneity hamper phenotype-genotype comparison. We report on two male adult siblings with the PMM2 mutation c.385G > A(p.v129M) and c.422G> A(p.R141H) and partiallly different clinical phenotype. Patient 2 has a more severe degree of neurological and systemic involvement and a more pronounced decrease in levels of serum glycoproteins. MALDI-TOF mass spectrometry of serum transferrin and alpha-1-antitrypsin shows more pronounced glycosylation defects in the more severely affected patient. Glycoproteomic analysis may reveal differences in CDG-la patients with different disease severity and might endorse clinical characterization of CDG-la patients. (C) 2008 Wiley-Liss, Inc.