A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases

Introduction-Congenital disorders of glycosylation (CDG), or carbohydrate d eficient glycoprotein syndromes, form a new group of multisystem disorders characterised by defective glycoprotein biosynthesis, ascribed to various b iochemical mechanisms. Methods-We report the clinical, biological, and molecular analysis of 26 CD G I patients, including 20 CDG Ia, two CDG Ib, one CDG Ic, and three CDG Ix , detected by western blotting and isoelectric focusing of serum transferri n. Results-Based on the clinical features, CDG Ia could be split into two subt ypes: a neurological form with psychomotor retardation, strabismus, cerebel lar hypoplasia, and retinitis pigmentosa (n=11), and a multivisceral form w ith neurological and extraneurological manifestations including Liver, card iac, renal, or gastrointestinal involvement (n=9). Interestingly, dysmorphi c features, inverted nipples, cerebellar hypoplasia, and abnormal subcutane ous fat distribution were not consistently observed in CDG Ia. By contrast, the two CDG Ib patients had severe liver disease, enteropathy, and hyperin sulinaemic hypoglycaemia but no neurological involvement. Finally, the CDG Ic patient and one of the CDG Ix patients had psychomotor retardation and s eizures. The other CDG Ix patients had severe proximal tubulopathy, bilater al cataract, and white matter abnormalities tone patient), or multiorgan fa ilure and multiple birth defects tone patient). Conclusions-Owing to the remarkable clinical variability of CDG, this novel disease probably remains largely underdiagnosed. The successful treatment of CDG ib patients with oral mannose emphasises the paramount importance of early diagnosis of PMI deficiency.