title: Screening of lysosomal storage disorders: application of the online trapping-and-cleanup liquid chromatography/mass spectrometry method for mucopolysaccharidosis I.
abstract: In recent years, new treatments have become available to treat some lysosomal storage disorders (LSDs) and many studies suggest that there is a benefit with starting therapy early. Newborn screening should detect diseases early enough for prompt treatment. Some countries include additional conditions, such as some LSDs, into their newborn screening panels. Mucopolysaccharidosis Type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α-L-iduronidase (IDUA) activity. Currently, enzyme replacement therapy (ERT) or bone marrow transplantation is available and this has raised a growing interest for the development of a newborn screening test. In 2009, we reported a new fast and simplified tandem mass spectrometry-based method for quantifying five enzyme activities on dried blood spots. Here, we describe the inclusion of IDUA activity determination for the simultaneous detection of six lysosomal storage diseases. We have defined reference normal ranges by testing 680 healthy newborns and 240 adults. The assay was checked through three confirmed MPS I patients whose IDUA activity was below the normal range. Reproducibility of the assays has been established by assessing the intra-day and inter-day assay imprecisions. This quick assay has been devised to be implemented in newborn screening by liquid chromatography tandem mass spectrometry.
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy and Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ombrone
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy and Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy and Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giocaliere
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Della Bona
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Forni
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Villanelli
authors.affiliation: AB Sciex Italia srl, Via Lombardia 218, 20861 Brugherio, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Casetta
authors.affiliation: Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Newborn Screening, Biochemistry and Pharmacology Laboratories, Clinic of Pediatric Neurology, Meyer University Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy, Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Viale Pieraccini 24, 50139 Florence, Italy and Paediatric Neurology Unit and Laboratories, Neuroscience Department, Meyer Children's Hospital, 24 Viale Pieraccini 24, 50139 Florence, Italy. giancarlo.lamarca@unifi.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D059788:Dried Blood Spot Testing / Q000379:methods* / Q000592:standards; D006801:Humans; D007068:Iduronidase / Q000032:analysis / Q000097:blood / Q000737:chemistry; D007231:Infant, Newborn; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D008059:Mucopolysaccharidosis I / Q000175:diagnosis*; D015997:Neonatal Screening / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D007068:Iduronidase