Composition and structure of glycosaminoglycans in DBS from 2-3-day-old newborns for the diagnosis of mucopolysaccharidosis.

Abstract

Dried blood spot (DBS) technology is a cheap and easy method largely applied in newborn screening. Mucopolysaccharidoses (MPS) are characterized by the deficit of enzymes that degrade glycosaminoglycans (GAGs) characterized by progressive worsening of the conditions. For a possible early diagnosis of MPS, we developed a method of uronic acid (UA)-GAGs determination in DBS of 600 healthy newborns and from a small group of MPS subjects matched for age. Spotted blood UA-GAGs of the normal newborns are composed of 67.2% chondroitin sulfate (CS), 28.6% heparan sulfate (HS) and 4.4% hyaluronic acid with a CS/HS ratio of 2.35 and a total GAGs content of 0.43 μg/DBS. A chemical evaluation of CS and HS structure was performed by measuring their disaccharide composition, sulfation and the overall charge density. The DBS of four different MPS types presented an increase of total or single UA-GAGs content and/or modifications of the CS and HS disaccharide composition as well as chemical signature also related to the MPS enzymatic defect. The modifications of the UA-GAGs composition, parameters and structure of healthy newborns determined in DBS would be useful for a possible early diagnosis of various MPS types.

• Authors: Francesca Maccari, Fabio Galeotti, Veronica Mantovani, Lucia Zampini, Lucia Padella, Laura Rigon, Daniela Concolino, Agata Fiumara, Elisa Pascale, Annarita Pittalà, Tiziana Galeazzi, Chiara Monachesi, Rita Lucia Marchesiello, Giovanni Coppa, Orazio Gabrielli, Nicola Volpi
• Journal: Analytical biochemistry (Anal Biochem) Vol. 557 Pg. 34-41 (09 15 2018) ISSN: 1096-0309 [Electronic] United States
• PMID: 30009765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Glycosaminoglycans

Topics

• Carbohydrate Conformation
• Dried Blood Spot Testing
• Glycosaminoglycans (blood, chemistry)
• Humans
• Infant, Newborn
• Mucopolysaccharidoses (blood, diagnosis)