Newborn screening for lysosomal storage disorders.
Lysosomal storage disorders (LSD) are chronic progressive diseases that have a devastating impact on the patient and family. Most patients are clinically normal at birth but develop symptoms early in childhood. Despite no curative treatment, a number of therapeutic options are available to improve quality of life. To achieve this, there is a pressing need for newborn screening to identify affected individuals early, before the onset of severe irreversible pathology. We have developed a multiplexed immune-quantification assay of 11 different lysosomal proteins for the identification of individuals with an LSD and evaluated this assay in a retrospective study using blood-spots from; newborns subsequently diagnosed with an LSD (n=19, six different LSD), individuals sampled after diagnosis of an LSD (n=92, 11 different LSD), newborn controls (n=433), and adult controls (n=200). All patients with mucopolysaccharidosis type I (MPS I), MPS II, MPS IIIA, MPS VI, metachromatic leukodystrophy, Niemann-Pick disease type A/B, and multiple sulfatase deficiency could be identified by reduced enzyme levels compared to controls. All mucolipidosis type II/III patients were identified by the elevation of several lysosomal enzymes, above the control range. Most Fabry, Pompe, and Gaucher disease patients were identified from either single protein differences or profiles of multiple protein markers. Newborn screening for multiple LSD is achievable using multiplexed immune-quantification of a panel of lysosomal proteins. With further validation, this method could be readily incorporated into existing screening laboratories and will have a substantial impact on patient management and counseling of families.
Meikle
Peter J
PJ
Lysosomal Diseases Research Unit, Department of Genetic Medicine, Children Youth and Women's Health Service, North Adelaide, South Australia 5006, Australia. peter.meikle@adelaide.edu.au
Grasby
Dallas J
DJ
Dean
Caroline J
CJ
Lang
Debbie L
DL
Bockmann
Michelle
M
Whittle
Alison M
AM
Fietz
Michael J
MJ
Simonsen
Henrik
H
Fuller
Maria
M
Brooks
Douglas A
DA
Hopwood
John J
JJ
D000328:Adult; D016022:Case-Control Studies; D006801:Humans; D007231:Infant, Newborn; D016464:Lysosomal Storage Diseases / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology; D015997:Neonatal Screening; D011506:Proteins / Q000032:analysis / Q000276:immunology; D012189:Retrospective Studies
D011506:Proteins; C018589:lysosomal proteins