title: First pilot newborn screening for four lysosomal storage diseases in an Italian region: identification and analysis of a putative causative mutation in the GBA gene.
abstract: We report the first newborn screening pilot study in an Italian region for four lysosomal disorders including Pompe disease, Gaucher disease, Fabry disease and mucopolysaccharidosis type 1. The screening has been performed using enzymatic assay on Dry Blood Spot on filter paper. A total of 3403 newborns were screened. One newborn showed a reduction of β-glucosidase activity in leucocytes. Molecular analysis revealed a status of compound heterozygous for the panethnic mutation N370S and for the sequence variation E388K, not yet correlated to Gaucher disease onset. The functional consequences of the E388K replacement on β-glucosidase activity were evaluated by in vitro expression, showing that the mutant protein retained 48% of wild type activity. Structural modeling predicted that the E388K replacement, localized to a surface of the enzyme, would change the local charges distribution which, in the native protein, displays an overwhelming presence of negative charges. However, the newborn, and a 4 year old sister showing the same genomic alterations, are currently asymptomatic. This pilot newborn screening for lysosomal diseases appears to be feasible and affordable to be extended to large populations. Moreover other lysosomal diseases for which a therapy is available or will be available, could be included in the screening.
authors: DSEEA, University of Perugia, Italy.
authors: Silvia
authors: S
authors: Paciotti
authors: Emanuele
authors: E
authors: Persichetti
authors: Severo
authors: S
authors: Pagliardini
authors: Marta
authors: M
authors: Deganuto
authors: Camillo
authors: C
authors: Rosano
authors: Chiara
authors: C
authors: Balducci
authors: Michela
authors: M
authors: Codini
authors: Mirella
authors: M
authors: Filocamo
authors: Anna Rita
authors: AR
authors: Menghini
authors: Veronica
authors: V
authors: Pagliardini
authors: Silvio
authors: S
authors: Pasqui
authors: Bruno
authors: B
authors: Bembi
authors: Andrea
authors: A
authors: Dardis
authors: Tommaso
authors: T
authors: Beccari
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D016464:Lysosomal Storage Diseases / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods*; D010865:Pilot Projects
chemical_list: D005962:Glucosylceramidase