Heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III.
BACKGROUND
Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders (LSDs) caused by a defect in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in MPS patients results in extensive, severe and progressive disease. Disease modifying therapy is available for three of the MPSs and is being developed for the other types. Early initiation of treatment, before the onset of irreversible tissue damage, clearly provides a favorable disease outcome. However, early diagnosis is difficult due to the rarity of these disorders in combination with the wide variety of clinical symptoms. Newborn screening (NBS) is probably the optimal approach, and several screening techniques for different MPSs have been studied. Here we describe a relatively simple and sensitive method to measure levels of dermatan and heparan sulfate derived disaccharides in dried blood spots (DBS) with HPLC-MS/MS, and show that this reliably separates MPS I, II and MPS III newborns from controls and heterozygotes.


METHODS
Newborn DBS of 11 MPS I, 1 MPS II, and 6 MPS III patients, with phenotypes ranging from severe to relatively attenuated, were collected and levels of dermatan and heparan sulfate derived disaccharides in these DBS were compared with levels in DBS of newborn MPS I and MPS III heterozygotes and controls.


RESULTS
The levels of dermatan and heparan sulfate derived disaccharides were clearly elevated in all newborn DBS of MPS I, II and III patients when compared to controls. In contrast, DBS of MPS I and III heterozygotes showed similar disaccharide levels when compared to control DBS.


CONCLUSIONS
Our study demonstrates that measurement of heparan and dermatan sulfate derived disaccharides in DBS may be suitable for NBS for MPS I, II and MPS III. We hypothesize that this same approach will also detect MPS VI, and VII patients, as heparan sulfate and/or dermatan sulfate is also the primary storage products in these disorders.
Department of Pediatrics and Amsterdam Lysosome Centre Sphinx, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Jessica
J
de Ruijter
Minke H
MH
de Ru
Tom
T
Wagemans
Lodewijk
L
Ijlst
Allan M
AM
Lund
Paul J
PJ
Orchard
G Bradley
GB
Schaefer
Frits A
FA
Wijburg
Naomi
N
van Vlies
D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003871:Dermatan Sulfate / Q000031:analogs & derivatives* / Q000097:blood; D004187:Disaccharides / Q000097:blood*; D006497:Heparan Sulfate / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009083:Mucopolysaccharidoses / Q000097:blood / Q000175:diagnosis*; D008059:Mucopolysaccharidosis I / Q000097:blood / Q000175:diagnosis; D016532:Mucopolysaccharidosis II / Q000097:blood / Q000175:diagnosis; D009084:Mucopolysaccharidosis III / Q000097:blood / Q000175:diagnosis; D015997:Neonatal Screening; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D003871:Dermatan Sulfate; D004187:Disaccharides; D006497:Heparan Sulfate