title: IGF system in children with congenital disorders of glycosylation.
abstract: OBJECTIVE
  The function of IGF system components is affected by their glycosylation status in vitro. However, little is known about the role of glycosylation status of these components in vivo. In this study we determined the impact of glycosylation on the endocrine IGF system in children with the rare syndrome of congenital disorders of glycosylation (CDG).
  
  
  METHODS
  Analyses of serum samples from children with CDG and healthy controls.
  
  
  METHODS
  Children with CDG (N = 12) were recruited as part of a separate clinical study of mannose therapy at the Mayo Clinic. Serum from control children (N = 11) were obtained as routine samples before discard.
  
  
  METHODS
  Levels and glycosylation state of components of the IGF system and ability to form physiologically relevant ternary complexes composed of IGF, IGFBP-3, and an acid-labile subunit (ALS).
  
  
  RESULTS
  Serum levels of IGF-1, IGF-2, ALS, and IGFBP-3 were reduced (P < 0.05) in children with CDG when compared to controls. Immunoblot analysis showed incomplete glycosylation of ALS and IGFBP-3 and impaired ternary complex formation in CDG. Partial normalization of ALS and IGFBP-3 glycosylation was associated with improvement in linear growth in a child with CDG-Ib during initiation of oral mannose therapy.
  
  
  CONCLUSIONS
  Inadequate glycosylation of IGFBP-3 and ALS has a negative effect on the function of these proteins in vivo. This study provides the first evidence in humans for the importance of glycosylation on components of the IGF system.
authors.affiliation: Division of Pediatric Endocrinology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Miller
authors.forename: M Javad
authors.initials: MJ
authors.lastname: Khosravi
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000097:blood / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II