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The combined use of enzyme activity and metabolite assays as a strategy for newborn screening of mucopolysaccharidosis type I
| Content Provider | Scilit |
|---|---|
| Author | Polo, Giulia Gueraldi, Daniela Giuliani, Antonella Rubert, Laura Cazzorla, Chiara Salviati, Leonardo Marzollo, Antonio Biffi, Alessandra Burlina, Alessandro P. Burlina, Alberto B. |
| Copyright Year | 2020 |
| Abstract | Objectives: Mucopolysaccharidosis type I (MPS I) was added to our expanded screening panel in 2015. Since then, 127,869 newborns were screened by measuring α-L-iduronidase (IDUA) enzyme activity with liquid chromatography tandem mass spectrometry (LC-MS/MS). High false positives due to frequent pseudodeficiency alleles prompted us to develop a second-tier test to quantify glycosaminoglycan (GAG) levels in dried blood spot (DBS). Methods: Heparan-sulfate (HS) and dermatan-sulfate (DS) were measured with LC-MS/MS after methanolysis. DBSs were incubated with methanolic-HCl 3 N at 65 °C for 45 min. Chromatographic separation used an amide column with a gradient of acetonitrile and water with 10 mM ammonium acetate in a 9-min run. The method was validated for specificity, linearity, lower limit of quantification (LOQ), accuracy and precision. Results: Intra- and inter-day coefficients of variation were <15% for both metabolites. Reference values in 40 healthy newborns were: HS mean 1.0 mg/L, 0–3.2; DS mean 1.5 mg/L, 0.5–2.7). The two confirmed newborn MPS I patients had elevated HS (4.9–10.4 mg/L, n.v. <3.2) and DS (7.4–8.8 mg/L, n.v. <2.7). Since its introduction in February 2019, the second-tier test reduced the recall rate from 0.046% to 0.006%. Among 127,869 specimens screened, the incidence was 1:63,935 live births. Both patients started enzyme replacement therapy (ERT) within 15 days of birth and one of them received allogenic hematopoietic stem cell transplantation (HSCT) at ht age of 6 months. Conclusions: GAGs in DBS increased the specificity of newborn screening for MPS I by reducing false-positives due to heterozygosity or pseudodeficiency. Early diagnosis and therapeutical approach has improved the outcome of our patients with MPS I. |
| Related Links | https://www.degruyter.com/downloadpdf/journals/cclm/ahead-of-print/article-10.1515-cclm-2020-0064/article-10.1515-cclm-2020-0064.pdf |
| Ending Page | 2072 |
| Page Count | 10 |
| Starting Page | 2063 |
| ISSN | 14346621 |
| e-ISSN | 14374331 |
| DOI | 10.1515/cclm-2020-0064 |
| Journal | Clinical Chemistry and Laboratory Medicine (CCLM) |
| Issue Number | 12 |
| Volume Number | 58 |
| Language | English |
| Publisher | Walter de Gruyter GmbH |
| Publisher Date | 2020-05-08 |
| Access Restriction | Open |
| Subject Keyword | Clinical Chemistry and Laboratory Medicine (cclm) Pediatrics and Child Health Dermatan Sulfate Expanded Newborn Screening Glycosaminoglycans Heparan Sulfate Lc-ms/ms Lysosomal Disorders Lysosomal Disorders Newborn Screening Mucopolysaccharidosis Type I Second-tier Test Tandem Mass Spectrometry Journal: Clinical Chemistry and Laboratory Medicine (CCLM), Vol- 58 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry (medical) Clinical Biochemistry |
