A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency.
Three siblings suffered from an unusual disorder of cyclic vomiting and congenital hepatic fibrosis. Serum transferrin isoelectric focusing showed increased asialo- and disialotransferrin isoforms as seen in the carbohydrate-deficient glycoprotein (CDG) syndrome type I. Phosphomannomutase, which is deficient in most patients with type I CDG syndrome, was found to be normal in all three patients. Structural analysis of serum transferrin revealed nonglycosylated, hypoglycosylated, and normoglycosylated transferrin molecules. These findings suggested a defect in the early glycosylation pathway. Phosphomannose isomerase was found to be deficient and the defect was present in leucocytes, fibroblasts, and liver tissue. Phosphomannose isomerase deficiency appears to be a novel glycosylation disorder, which is biochemically indistinguishable from CDG syndrome type I. However, the clinical presentation is entirely different.
de Koning
T J
TJ
Department of Metabolic Diseases, University Children's Hospital "Het Wilhelmina Kinderzieken-huis,", Utrecht, The Netherlands.
Dorland
L
L
van Diggelen
O P
OP
Boonman
A M
AM
de Jong
G J
GJ
van Noort
W L
WL
De Schryver
J
J
Duran
M
M
van den Berg
I E
IE
Gerwig
G J
GJ
Berger
R
R
Poll-The
B T
BT
D000293:Adolescent; D002648:Child; D018981:Congenital Disorders of Glycosylation / Q000145:classification / Q000235:genetics; D005260:Female; D005632:Fructose / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008297:Male; D008358:Mannose / Q000378:metabolism; D008359:Mannose-6-Phosphate Isomerase / Q000172:deficiency* / Q000235:genetics; D017875:Phosphotransferases (Phosphomutases) / Q000032:analysis; D014168:Transferrin / Q000032:analysis
D014168:Transferrin; D005632:Fructose; D008359:Mannose-6-Phosphate Isomerase; D017875:Phosphotransferases (Phosphomutases); C052799:phosphomannomutase; D005947:Glucose; D008358:Mannose