title: Diagnosing lysosomal storage disorders: mucopolysaccharidosis type I.
abstract: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder due to deficiency of alpha iduronidase (IDUA). Progressive storage of dermatan and heparan sulfate throughout the body lead to a multiorgan presentation including short stature, dysostosis multiplex, corneal clouding, hearing loss, coarse facies, hepatosplenomegaly, and intellectual disability. Diagnosis of MPS I is based on IDUA enzyme analysis in leukocytes or dried blood spots (DBS) followed by molecular confirmation of the IDUA gene mutations in individuals with low enzyme activity. The advent of mass spectrometry methods for enzyme analysis in DBS has enabled high-throughput screening for MPS I in symptomatic individuals and newborn infants. The following unit provides the detailed analytical protocol for measurement of IDUA activity in DBS using tandem mass spectrometry.
authors.affiliation: Division of Clinical and Translational Genetics, Dr. John T. MacDonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Britt A
authors.initials: BA
authors.lastname: Johnson
authors.affiliation: Division of Clinical and Translational Genetics, Dr. John T. MacDonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Angela
authors.initials: A
authors.lastname: Dajnoki
authors.affiliation: Division of Clinical and Translational Genetics, Dr. John T. MacDonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Olaf A
authors.initials: OA
authors.lastname: Bodamer
mesh_terms: D003871:Dermatan Sulfate / Q000096:biosynthesis; D059788:Dried Blood Spot Testing / Q000295:instrumentation / Q000379:methods*; D056947:Enzyme Replacement Therapy; D015870:Gene Expression; D006497:Heparan Sulfate / Q000096:biosynthesis; D006801:Humans; D007068:Iduronidase / Q000172:deficiency* / Q000235:genetics / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000201:enzymology; D008059:Mucopolysaccharidosis I / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D015997:Neonatal Screening; D053719:Tandem Mass Spectrometry
chemical_list: D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D007068:Iduronidase
keywords: Hurler Syndrome; MPS I; Mucopolysaccharidosis type I; Scheie Syndrome; alpha-iduronidase; dried blood spot; tandem mass spectrometry