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

详细信息    查看全文

• 作者：Silvia Paciotti ; Emanuele Persichetti ; Severo Pagliardini ; Marta Deganuto ; Camillo Rosano ; Chiara Balducci ; Michela Codini ; Mirella Filocamo ; Anna Rita Menghini ; Veronica Pagliardini ; Silvio Pasqui ; Bruno Bembi ; Andrea Dardis ; Tommaso Beccari
• 关键词：LSD ; lysosomal storage disease ; ERT ; enzyme replacement therapy ; DBS ; dried blood spots ; GBA ; acid ¦Â-glucosidase ; GAA ; acid ¦Á-glucosidase ; GLA ; acid ¦Á-galactosidase ; GD ; Gaucher disease ; IDUA ; ¦Á-l-iduronidase ; MPS ; mucopolysaccharidosis
• 刊名：Clinica Chimica Acta
• 出版年：2012
• 出版时间：20 November, 2012
• 年：2012
• 卷：413
• 期：23-24
• 页码：1827-1831
• 全文大小：379 K

文摘

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 ¦Â-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 ¦Â-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.