Congenital disorder of glycosylation type Id: clinical phenotype, molecular analysis, prenatal diagnosis, and glycosylation of fetal proteins.
Congenital disorder of glycosylation type Id is an inherited glycosylation disorder based on a defect of the first mannosyltransferase involved in N-glycan biosynthesis inside the endoplasmic reticulum. Only one patient with this disease has been described until now. In this article, a second patient and an affected fetus are described. The patient showed abnormal glycosylation of several plasma proteins as demonstrated by isoelectric focusing and Western blot. Lipid-linked oligosaccharides in the endoplasmic reticulum, reflecting early N-glycan assembly, revealed an accumulation of immature Man(5)GlcNAc(2)-glycans in fibroblasts of the patient. Chorion cells of the affected fetus showed the same characteristic lipid-linked oligosaccharides pattern. However, the fetus had a normal glycosylation of several plasma proteins. Some fetal glycoproteins are known to be derived from the mother, but even glycoproteins that do not cross the placenta were normally glycosylated in the affected fetus. Maternal or placental factors that partially compensate for the glycosylation defect in the fetal stage must be proposed and may be relevant for the therapy of these disorders in the future.
Denecke
Jonas
J
Department of Pediatrics, University Hospital of Münster, 48149 Münster, Germany. deneckj@uni-muenster.de
Kranz
Christian
C
von Kleist-Retzow
Juergen Ch
JCh
Bosse
Kristin
K
Herkenrath
Peter
P
Debus
Otfried
O
Harms
Erik
E
Marquardt
Thorsten
T
D017398:Alternative Splicing; D015153:Blotting, Western; D002239:Carbohydrate Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005326:Fetal Proteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007525:Isoelectric Focusing; D008055:Lipids / Q000737:chemistry; D008297:Male; D008364:Mannosyltransferases / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D009844:Oligosaccharides / Q000737:chemistry; D010641:Phenotype; D011134:Polysaccharides / Q000737:chemistry; D011296:Prenatal Diagnosis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014168:Transferrin / Q000096:biosynthesis
D005326:Fetal Proteins; D008055:Lipids; D009844:Oligosaccharides; D011134:Polysaccharides; D014168:Transferrin; C489947:ALG3 protein, human; D008364:Mannosyltransferases