Congenital disorder of glycosylation IId (CDG-IId) -- a new entity: clinical presentation with Dandy-Walker malformation and myopathy.

A 1.5-year-old boy with macrocephaly due to a Dandy-Walker malformation presented with progressive hydrocephalus, extensive muscular hypotonia, transient cholestatic syndrome, extensive coagulation abnormalities and elevated creatine kinase indicating myopathy. Diagnostic work-up indicated a congenital disorder of glycosylation (CDG, formerly carbohydrate deficient glycoprotein syndrome). The serum transferrin pattern obtained by automated isoelectric focusing (IEF) showed an hitherto unreported pattern with strongly elevated tri-, di-, mono- and asialotransferrin bands, increasing in this order together with markedly decreased tetrasialotransferrin. Investigation of two additional glycoproteins, alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, confirmed a generalised defect of glycosylation. All known glycosylation defects could be ruled out by enzymatic analyses in either leukocytes or fibroblasts or by the results obtained by IEF. SDS-electrophoresis demonstrated a marked difference in the molecular weight of transferrin, suggesting the lack of parts or of all oligosaccharide chains. The defect could be delineated to a deficiency of beta-1,4-galactosyltransferase (E.C.2.4.1.38) due to a homozygous insertion (1031 - 1032 insC). Details of the biochemical and molecular findings will be described elsewhere.