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.
Peters
V
V
Universitäts-Kinderklinik, Sektion für Metabolische und Endokrinologische Erkrankungen, Heidelberg, Germany. Verena_Peters@med.uni-heidelberg.de
Penzien
J M
JM
Reiter
G
G
Körner
C
C
Hackler
R
R
Assmann
B
B
Fang
J
J
Schaefer
J R
JR
Hoffmann
G F
GF
Heidemann
P H
PH
D000293:Adolescent; D018981:Congenital Disorders of Glycosylation / Q000150:complications* / Q000175:diagnosis*; D003616:Dandy-Walker Syndrome / Q000150:complications*; D006801:Humans; D008297:Male; D009135:Muscular Diseases / Q000150:complications*