Nationwide Newborn Screening Program for Mucopolysaccharidoses in Taiwan and an Update of the “Gold Standard” Criteria Required to Make a Confirmatory Diagnosis

Chih-Kuang Chuang,Hsiao-Jan Chen,Ya-Hui Chang,Fran Sisca,Chung-Lin Lee,Yun-Ting Lo,Hsiang-Yu Lin,Ru-Yi Tu,Shu-Min Kao,Mei-Ying Liu,Li-Yun Wang,Hsin-Yun Liu,Shuan-Pei Lin,Huey-Jane Ho

doi:10.3390/diagnostics11091583

Abstract

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases (LSDs) caused by an inherited gene defect. MPS patients can remain undetected unless the initial signs or symptoms have been identified. Newborn screening (NBS) programs for MPSs have been implemented in Taiwan since 2015, and more than 48.5% of confirmed cases of MPS have since been referred from these NBS programs. The purpose of this study was to report the current status of NBS for MPSs in Taiwan and update the gold standard criteria required to make a confirmative diagnosis of MPS, which requires the presence of the following three laboratory findings: (1) elevation of individual urinary glycosaminoglycan (GAG)-derived disaccharides detected by MS/MS-based assay; (2) deficient activity of a particular leukocyte enzyme by fluorometric assay; and (3) verification of heterogeneous or homogeneous variants by Sanger sequencing or next generation sequencing. Up to 30 April 2021, 599,962 newborn babies have been screened through the NBS programs for MPS type I, II, VI, and IVA, and a total of 255 infants have been referred to MacKay Memorial Hospital for a confirmatory diagnosis. Of these infants, four cases were confirmed to have MPS I, nine cases MPS II, and three cases MPS IVA, with prevalence rates of 0.67, 2.92, and 4.13 per 100,000 live births, respectively. Intensive long-term regular physical and laboratory examinations for asymptomatic infants with confirmed MPS or with highly suspected MPS can enhance the ability to administer ERT in a timely fashion.

Highlights

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases caused by mutations of genes encoding for lysosomal enzymes leading to defects in the stepwise degradation of glycosaminoglycans (GAGs)
In Newborn screening (NBS) for MPS, the goals are early detection, making an early diagnosis, and providing early therapy to effectively prevent the development of irreversible clinical manifestations
The diagnostic age has been lowered from 4.3 years to 0.2 years, allowing the possibility of providing enzyme replacement therapy (ERT) in a timely fashion and preventing severe and irreversible symptoms

Summary

Introduction

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases caused by mutations of genes encoding for lysosomal enzymes leading to defects in the stepwise degradation of glycosaminoglycans (GAGs). Clinical manifestations of MPS are chronic and progressive. MPS patients present with many distinct clinical features including organomegaly, developmental delay, dysmorphic facial features, skeletal dysplasia (dysostosis multiplex), and growth retardation. The clinical features of MPS may present from birth to late childhood or even early adulthood depending on the severity of the MPS phenotype. Death from respiratory or cardiac failure and respiratory infections usually occurs before the age of 10 years in patients with severe phenotypes [1,2,3,4]. Pilot newborn screening (NBS) programs for MPS I, II, IVA, and VI have been progressively implemented in Taiwan since 2015, and 48% (16/33) of patients diagnosed with MPS between 2016 and 2019 were referred from these NBS programs. The median age at diagnosis of these newborns was 0.2 years, which is notably lower than the median age of 4.3 years in the other 159 patients who were diagnosed due to clinical indications [5]

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