Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb 3;15(1):38.
doi: 10.1186/s13023-020-1322-z.

Newborn screening for Morquio disease and other lysosomal storage diseases: results from the 8-plex assay for 70,000 newborns

Yin-Hsiu Chien  1   2 , Ni-Chung Lee  1   2 , Pin-Wen Chen  1 , Hui-Ying Yeh  1 , Michael H Gelb  3 , Pao-Chin Chiu  4 , Shao-Yin Chu  5 , Chen-Hao Lee  6 , An-Ru Lee  1 , Wuh-Liang Hwu  7   8
Affiliations

Newborn screening for Morquio disease and other lysosomal storage diseases: results from the 8-plex assay for 70,000 newborns

Yin-Hsiu Chien et al. Orphanet J Rare Dis. .

Abstract

Background: The necessity of early treatment for lysosomal storage diseases (LSDs) has triggered the development of newborn screening for LSDs in recent years. Here we report the first 70,000 newborns screened for Mucopolysaccharidosis (MPS) type 4A (Morquio syndrome) and other LSDs by an 8-plex assay including the original 4-plex LSD screening tandem mass spectrometry (MS/MS) assay for Pompe disease, Fabry disease, Gaucher disease, and MPS I disease.

Methods: The additional reaction for MPS II, MPS 3B, MPS 4A, and MPS 6 enzymes was performed separately from the 4-plex reaction. The two reactions were quenched and extracted, then combined before carrying out a single 2-min UPLC-MS/MS analysis.

Results: From Mar. 2018 to Apr. 2019, 73,743 newborns were screened with the 8-plex LSD screening assay. The 8-plex assay revealed a better analytical precision than the previous 4-plex assay possibly because the 8-plex was carried out using UPLC-MS/MS. Six newborns were found to have low MPS-4A enzyme (N-acetylgalactosamine-6-sulfatase) activity and biallelic GALNS pathogenic mutations in trans; these patients are presumably affected with MPS4A, making an incidence of one in 12,291 (95% confident interval (CI): 5633-26,817). One mutation, c.857C > T (p.T286 M) of the GALNS gene, accounted 5 of the 12 mutated alleles. These newborns had immature vertebral bodies at 1 month of age, and one case was treated with elosulfase alfa 2 mg/kg/week starting from 4 months of age. Among other MPSs screened, one case of MPS I, 3 cases of MPS II, and 3 cases of MPS 3B were detected. One case of mucolipidosis type III was also diagnosed. In conjunction with another 9 patients of Pompe disease, Gaucher disease, and classical Fabry disease, making an incidence of LSDs as one in 3206 newborns (95% CI: 2137 - 4811). The one with infantile-onset Pompe disease and the one with Gaucher disease were treated since the age of 8 days and 41 days respectively.

Conclusions: Routine newborn screening of MPS 4A and other LSDs were made possible by the 8-plex LSD screening assay. However, detailed phenotype prediction and the time to start treatment will need further elucidation.

Keywords: Lysosomal storage disease; MPS4A; Morquio disease; Mucopolysaccharidosis; Multiplex newborn screening; Tandem mass spectrometry.

PubMed Disclaimer

Conflict of interest statement

YHC and WLH have received consulting and advisor fees from Biomarin and Sanofi, and receive research funding from Biomarin and Sanofi. M. H. Gelb serves as a consultant for PerkinElmer and gets funding from Takeda, Biomarin, Ultrageneyx, The Legacy of Angels Foundation and CureGM1 Foundation. Others report no competing interests.

Figures

Fig. 1
Fig. 1
Thoracolumbar spine lateral views from three cases positive for MPS 4A screening (Case 1–3), one case positive for MPS I, and one case positive for ML III at ages 1–1.5 months. Abnormal findings in MPS 4A patients include incomplete fusion of the rostral and caudal halves of the vertebrae (black arrows), and ‘bone within bone’ appearance (white arrows); these findings are not seen in the MPS I or ML III patients. The images were rescaled and flipped for easy comparison
See this image and copyright information in PMC

References

    1. Liu Y, Yi F, Kumar AB, Kumar Chennamaneni N, Hong X, Scott CR, et al. Multiplex tandem mass spectrometry enzymatic activity assay for newborn screening of the Mucopolysaccharidoses and type 2 neuronal Ceroid Lipofuscinosis. Clin Chem. 2017;63(6):1118–1126. doi: 10.1373/clinchem.2016.269167. - DOI - PMC - PubMed
    1. Zhang XK, Elbin CS, Turecek F, Scott R, Chuang WL, Keutzer JM, et al. Multiplex lysosomal enzyme activity assay on dried blood spots using tandem mass spectrometry. Methods Mol Biol. 2010;603:339–350. doi: 10.1007/978-1-60761-459-3_32. - DOI - PMC - PubMed
    1. Kumar AB, Masi S, Ghomashchi F, Chennamaneni NK, Ito M, Scott CR, et al. Tandem mass spectrometry has a larger analytical range than fluorescence assays of Lysosomal enzymes: application to newborn screening and diagnosis of Mucopolysaccharidoses types II, IVA, and VI. Clin Chem. 2015;61(11):1363–1371. doi: 10.1373/clinchem.2015.242560. - DOI - PMC - PubMed
    1. Elliott S, Buroker N, Cournoyer JJ, Potier AM, Trometer JD, Elbin C, et al. Pilot study of newborn screening for six lysosomal storage diseases using tandem mass spectrometry. Mol Genet Metab. 2016;118(4):304–309. doi: 10.1016/j.ymgme.2016.05.015. - DOI - PMC - PubMed
    1. Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, et al. Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>a (IVS4+919G>a) Hum Mutat. 2009;30(10):1397–1405. doi: 10.1002/humu.21074. - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources