Single Screening of Newborns for 8 Lysosomal Storage Diseases, Including MPS, Possible

Single Screening of Newborns for 8 Lysosomal Storage Diseases, Including MPS, Possible
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Researchers have developed an efficient way of screening newborns for eight lysosomal storage diseases — including five mucopolysaccharidosis (MPS) disorders — at the same time, a large Taiwanese study shows.

The work suggests that this method could be used in newborn screening around the world to detect these disorders and initiate appropriate care following a positive diagnosis.

The study, “Newborn screening for Morquio disease and other lysosomal storage diseases: results from the 8-plex assay for 70,000 newborns,” was published in the Orphanet Journal of Rare Diseases.

Lysosomal storage diseases are inherited metabolic diseases characterized by an abnormal buildup of toxic molecules inside lysosomes — cellular compartments responsible for breaking down and recycling molecules — as a result of enzyme deficiencies. These disorders may affect different parts of the body, including bones, the heart, and central nervous system (brain and spinal cord).

MPS is an umbrella term for a group of lysosomal storage diseases caused by deficiencies in enzymes responsible for breaking down glycosaminoglycans (GAGs), long complex sugar molecules. MPS can be categorized into seven clinically distinct forms (and numerous subtypes) that vary in terms of age of onset, symptoms, and severity.

Given that lysosomal storage diseases often lead to irreversible damage, it is essential to detect them as early as possible to initiate treatment and potentially halt disease progression. For this reason, a simple and reliable way of screening newborns to detect the presence of several of these diseases simultaneously would save time, reduce costs, and allow early start of treatment.

Researchers in Taiwan developed a reliable method of screening newborns for eight lysosomal storage diseases — including five MPS disorders — and reported the results of its use over one year.

Taiwan added a multiple diagnostic test able to assess four — MPS I, Pompe disease, Fabry disease, and Gaucher disease — to its newborn screening program in 2015. The test was updated in 2018 to include four new MPS disorders: MPS II (Hunter syndrome), MPS IIIB (Sanfilippo syndrome type B) , MPS IVA (Morquio A syndrome), and MPS VI (Maroteaux-Lamy syndrome).

The new test can detect defects in specific enzymes associated with these eight LSDs using dried blood spots on a filter card — an easy way of collecting, shipping, and storing blood samples.

It is based on a powerful method, called ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS), which separates all the molecules in a sample and detects their levels of activity with a high degree of specificity and sensitivity.

Using this test, 73,743 newborns were screened between March 2018 and April 2019. In total, 76 of these infants (0.1%) screened positive for enzymatic deficiencies, and a diagnosis was confirmed in 23 of them (30.3%) through genetic or biomarker testing.

Among MPS, six newborns showed data consistent with an MPS IVA diagnosis, three had MPS IIIB (potentially mild), three had MPS II, and one was diagnosed with MPS I (potentially severe). There was also a case of mucolipidosis type III, an LSD closely related to a type of MPS I called Hurler syndrome.

Overall, the total frequency of MPS disorders was of 1 in 7,374 newborns (range 4,006 to 13,575).

Notably, this was the first large-scale newborn screening study for MPS IVA, and the researchers noted that its frequency was surprisingly high — 1 in 12,291 newborns (range 5,633 to 26,817). However, the incidence of severe MPS IVA (absence of enzymatic activity) — 1 in 73,743 newborns (range 13,020 to 417,750) — was more compatible with that previously reported in Taiwan (1 in 300,000 births).

“Our current study reveals that previous estimates of the incidence of MPS 4A in Taiwan may be underestimated, especially the mild phenotypes,” the researchers wrote.

Four newborns were also diagnosed with Pompe disease, four with Fabry disease, and one with Gaucher disease. The overall incidence for all tested lysosomal storage diseases was 1 in 3,206 newborns (range 2,137 to 4,811).

Researchers noted that the new test produced more precise results than the previous one, possibly due to UPLC-MS/MS use.

They also emphasized that follow-up studies on babies diagnosed with MPS 4A are required to better predict their disease course and severity, and to assess the benefits of early treatment.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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