Abstract
Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, is a lysosomal storage disorder (LSD) caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS). MPS II satisfies all criteria defined by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) for inclusion in the Recommended Uniform Screening Panel (RUSP) for newborn screening, apart from the fact that only minimal prospective population screening data are available. This report details the analytical validation, clinical validation, and implementation of a fluorometric assay for measurement of IDS activity in newborn dried blood spot (DBS) specimens at the Missouri State Public Health Laboratory (MSPHL). The assay is performed in a microwell plate format requiring approximately 15 min of hands-on time per plate and an incubation time of two hours. The analytical validation of this assay included linearity, analytical sensitivity, precision, and carry-over testing. Clinical validation was completed using more than 5000 deidentified presumptive normal newborn DBS specimens as well as seven specimens from patients known to be affected with MPS II. Following validation, MSPHL began prospective screening using the IDS assay on 1 November 2018. In the first 18 months of screening (to 30 June 2020), 146,954 specimens were prospectively screened using the method. Two newborns were identified with severe Hunter syndrome and the assay had a presumptive positive rate of 0.022%.
Highlights
Rates of newborn screening (NBS) for lysosomal storage disorders (LSDs) in the United States have soared following the addition of Pompe disease (Glycogen storage disease type II) and Mucopolysaccharidosis Type I (MPS I) to the Secretary of the Department of Health and Human Services’ Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively [1,2]
Mucopolysaccharidosis type II (MPS II), is an X-linked lysosomal storage disorder characterized by a dysfunctional iduronate-2-sulfatase (IDS) enzyme
Conventional and hematopoietic stem cell transplantation (HSCT) are the primary therapy strategies for confirmed Mucopolysaccharidosis Type II (MPS II), but additional therapies such as intrathecal enzyme replacement therapy (ERT), substrate reduction therapy, and gene therapy are under investigation to improve efficacy of treatment of central nervous system (CNS) dysfunction
Summary
HSCT has shown efficacy in treating central nervous system (CNS) symptoms, with improved benefit when the transplant is performed early in life [8,9] For these reasons, identification of MPS II at birth is imperative for both severe and attenuated patients so that therapies can be initiated as soon as possible and the natural history of the disease can be modified [10,11]. By 30 June 2020, 146,954 samples had been screened and two newborns diagnosed with severe Hunter syndrome following positive first and second tier screens and positive confirmatory test results These studies demonstrate a rapid, reliable method for high throughput NBS of MPS II that can be implemented using equipment that is readily available in most public health laboratories
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