title: Dried blood spots allow targeted screening to diagnose mucopolysaccharidosis and mucolipidosis.
abstract: BACKGROUND
  As patients with different types of mucopolysaccharidosis (MPS) and mucolipidosis (ML) may present with overlapping clinical features - including coarse face, hepatosplenomegaly, bone dysplasia and claw-hand deformities, collectively also called 'MPS-like phenotype', enzymatic and/or molecular genetic analyses are indispensable for accurate diagnosis and applying specific therapy. In this prospective study, we screened patients with symptoms compatible with MPS for MPS I, II (males) and VI.
  
  
  METHODS
  Dried blood spots/specimens (DBS) were collected from 200 patients with an MPS-like phenotype and analysed for activities of α-iduronidase (IDUA), iduronate-2-sulphatase (IDS), and arylsulphatase B (ARSB), the enzymes deficient in mucopolysaccharidosis (MPS) type I, II and VI, respectively. For the samples with pathologic enzyme activity, mutational analysis was carried out using the same DBS.
  
  
  RESULTS
  Based on enzymatic analysis of 200 DBS samples, a total of 45 (22.5%) showed low activity; 17 for MPS I (8.5%), 11 for MPS II (5.5%) and 9 for MPS VI (4.5%). Enzyme activities were suggestive for ML II/III in 8 (4.0%) cases. For 41 (91.1%) samples, DNA could be extracted from the filter paper. Mutations were identified in 11 (64.7%), 11 (100%), 9 (100%) and 5 (62.5%) patients putatively diagnosed biochemically with MPS I, II, VI, and ML II/III, respectively.
  
  
  CONCLUSIONS
  DBS enzymatic analysis can be used to diagnose MPS/ML. Initial results should be confirmed by a second enzyme assay and/or by molecular genetic testing. Given the advantages of DBS over other sample types in terms of ease of collection, storage and transportation, DBS are particularly useful for screening patients with an MPS-like phenotype in regions lacking specialised laboratories. In order to ascertain the diagnosis in a large number of cases, patients should be assessed in parallel for at least MPS I, II and VI.
authors.affiliation: Metabolic Laboratory, Department of Paediatrics, Institute of Clinical Chemistry, Hamburg University Medical Centre, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: Paulina Nieves
authors.initials: PN
authors.lastname: Cobos
authors.forename: Cordula
authors.initials: C
authors.lastname: Steglich
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Lukacs
authors.forename: Andreas
authors.initials: A
authors.lastname: Gal