Congenital Disorder of Glycosylation Ia with Deficient Phosphomannomutase Activity but Normal Plasma Glycoprotein Pattern

Congenital disorders of glycosylation [CDG; previously carbohydrate-deficient glycoprotein syndrome (1)] represent a newly delineated group of inherited diseases (2). The CDG are now clearly classified in two groups including subgroups. CDG I, by far the most common type with >300 patients described in the literature, is characterized by defects in the assembly of dolichol pyrophosphate oligosaccharide and/or in the transfer of oligosaccharide from dolichol pyrophosphate to an Asn residue on the nascent proteins. The other group, CDG II, reflects defects in the processing of protein-bound glycans. Only a few cases have been described (1). The diagnosis of CDG I is based on biochemical changes involving a unique carbohydrate deficiency observed in serum transferrin (TRF). In healthy subjects, serum TRF is fully glycosylated, containing two N-glycan chains, whereas in CDG I patients, it is partially (one chain) or totally deglycosylated (3). This structural abnormality is associated with different enzyme deficiencies (4). The most common, subtype Ia, is a deficiency of phosphomannomutase (PMM; EC 5.4.2.8) (5) and is present in 70% of CDG I patients. The disease is linked to chromosome 16p13, and numerous missense mutations have been identified in the PMM2 gene (6)(7). The condition is an autosomal recessive multisystemic disorder affecting the nervous system and numerous organs, including the liver, …