Development of an assay for the detection of mucopolysaccharidosis type VI patients using dried blood-spots.
BACKGROUND
Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD), which is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase (4-sulfatase). MPS VI is characterized by severe skeletal abnormalities, somatic tissue pathology and early death. Treatment possibilities include bone marrow transplantation (BMT) and enzyme replacement therapy (ERT; currently in phase III clinical trial). Early diagnosis of MPS VI will allow treatment before the onset of irreversible pathology.


METHODS
Sensitive immune assays have been developed to detect 4-sulfatase protein and activity in normal control and MPS VI blood-spots.


RESULTS
Dried blood-spots from MPS VI patients contained no detectable 4-sulfatase protein and activity, compared to 3.5-21 microg/L of 4-sulfatase protein and 291-1298 nmol/min/L of activity for normal human controls. In this evaluation study, the assay was sensitive and 100% specific, allowing reliable detection of individuals with MPS VI.


CONCLUSIONS
The assays reported here have the potential to detect MPS VI patients using dried blood-spots.
Hein
Leanne K
LK
Lysosomal Diseases Research Unit, Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia.
Meikle
Peter J
PJ
Dean
Caroline J
CJ
Bockmann
Michelle R
MR
Auclair
Dyane
D
Hopwood
John J
JJ
Brooks
Doug A
DA
D016022:Case-Control Studies; D006801:Humans; D009085:Mucopolysaccharidosis IV / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D012680:Sensitivity and Specificity; D013429:Sulfatases / Q000097:blood
D013429:Sulfatases