First Three Years’ Experience of Mucopolysaccharidosis Type-I Newborn Screening in California - 23/11/23
Abstract |
Objective |
To report on the first 3 years of mucopolysaccharidosis type I (MPS I) newborn screening (NBS) in the large and diverse state of California.
Study design |
The California Genetic Disease Screening Program began universal NBS for MPS I on August 29, 2018. The screening uses a 2-tiered approach: an α-L-iduronidase (IDUA) enzyme activity assay followed by DNA sequencing for variants in the IDUA gene.
Results |
As of August 29, 2021, 1 295 515 California newborns were screened for MPS I. In tier 1 of screening, 329 (0.025%) had an IDUA enzyme measurement below the cutoff and underwent tier-2 IDUA DNA sequencing. After tier 2, 146 (0.011%) newborns were screen positive, all of whom were referred to a metabolic Special Care Center for follow-up. After long-term follow-up, 7 cases were resolved as severe MPS I (Hurler syndrome) and 2 cases as attenuated MPS I for an MPS I birth prevalence of 1/143 946. DNA sequencing identified 107 unique IDUA variants among a total of 524 variants; 65% were known pseudodeficiency alleles, 25% were variants of uncertain significance, and 10% were pathogenic variants.
Conclusions |
As a result of a 2-tiered NBS approach, 7 newborns diagnosed with Hurler syndrome had received early treatment for MPS I. Continuation of California's long-term follow-up program will be crucial for further understanding the complex genotype–phenotype relationships of MPS I.
Le texte complet de cet article est disponible en PDF.Keywords : mucopolysaccharidosis type I, α-L-iduronidase, IDUA, lysosomal storage disorder, NBS, newborn dried blood spot
Abbreviations : CLIR, DBS, ERT, GAGs, HSCT, IDUA, LTFU, MPS I, NBS, SCC, STFU, VUS
Plan
Some of the study data presented in this manuscript was previously presented as a poster presentation at the Association of Public Health Laboratories Newborn Screening Virtual Symposium, October 5-14, 2021 titled “First 2.5 Years' Experience of MPS I Newborn Screening in California”. |
Vol 263
Article 113644- décembre 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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