Report of Five Years of Experience in Neonatal Screening for Mucopolysaccharidosis Type I and Review of the Literature

Vincenza Gragnaniello; Daniela Gueraldi; Laura Rubert; Francesca Manzoni; Chiara Cazzorla; Antonella Giuliani; Giulia Polo; Leonardo Salviati; Alberto Burlina

doi:10.3390/ijns6040085

Report of Five Years of Experience in Neonatal Screening for Mucopolysaccharidosis Type I and Review of the Literature

Int J Neonatal Screen. 2020 Nov 2;6(4):85. doi: 10.3390/ijns6040085.

Authors

Vincenza Gragnaniello¹, Daniela Gueraldi¹, Laura Rubert¹, Francesca Manzoni¹, Chiara Cazzorla¹, Antonella Giuliani¹, Giulia Polo¹, Leonardo Salviati², Alberto Burlina¹

Affiliations

¹ Division of Inherited Metabolic Diseases, Department of Diagnostic Services, University Hospital of Padua, via Orus 2/B, 35129 Padua, Italy.
² Clinical Genetics Unit, Department of Diagnostic Services, University Hospital of Padua, via Giustiniani 2, 35129 Padua, Italy.

Abstract

Mucopolysaccharidosis type I (MPS I) is a progressive lysosomal storage disease, with neurological and visceral involvement, in which early diagnosis through newborn screening (NBS) and early treatment can improve outcomes. We present our first 5 years of experience with laboratory and clinical management of NBS for MPS I. Since 2015, we have screened 160,011 newborns by measuring α-L-iduronidase (IDUA) activity and, since 2019, glycosaminoglycans (GAGs) in dried blood spot (DBS) as a second-tier test. Positive screening patients were referred to our clinic for confirmatory clinical and molecular testing. We found two patients affected by MPS I (incidence of 1:80,005). Before the introduction of second-tier testing, we found a high rate of false-positives due to pseudodeficiency. With GAG analysis in DBS as a second-tier test, no false-positive newborns were referred to our clinic. The confirmed patients were early treated with enzyme replacement therapy and bone-marrow transplantation. For both, the clinical outcome of the disease is in the normal range. Our experience confirms that NBS for MPS I is feasible and effective, along with the need to include GAG assay as a second-tier test. Follow-up of the two positive cases identified confirms the importance of early diagnosis through NBS and early treatment to improve the outcome of these patients.

Keywords: dermatan sulfate; expanded newborn screening; glycosaminoglycans; heparan sulfate; lysosomal disorders; mucopolysaccharidosis type I; second-tier test; tandem mass spectrometry; α-L-iduronidase.