Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Kubaski, Francyne; Mason, Robert W.; Nakatomi, Akiko; Shintaku, Haruo; Xie, Liping; Vlies, Naomi N. van; Church, Heather J.; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M.; Tomatsu, Shunji

doi:10.1016/j.ymgme.2016.11.186

Cited by 4 publications

(17 citation statements)

References 41 publications

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“…Five thousand newborn spots were acquired prospectively by Gifu Prefecture, Japan . Twelve of these newborn infants had been predicted to become MPSI patients by the Gifu NBS protocol, but had not developed MPS symptoms after 2 years of follow‐up . These 12 were considered to have a “pseudo‐deficiency,” with low alpha‐L‐iduronidase (IDUA) enzyme but no symptoms .…”

Section: Methodsmentioning

confidence: 99%

“…Twelve of these newborn infants had been predicted to become MPSI patients by the Gifu NBS protocol, but had not developed MPS symptoms after 2 years of follow‐up . These 12 were considered to have a “pseudo‐deficiency,” with low alpha‐L‐iduronidase (IDUA) enzyme but no symptoms . Separately, newborn DBS were obtained retrospectively for seven known nonattenuated MPSI patients .…”

Section: Methodsmentioning

confidence: 99%

“…These 12 were considered to have a “pseudo‐deficiency,” with low alpha‐L‐iduronidase (IDUA) enzyme but no symptoms . Separately, newborn DBS were obtained retrospectively for seven known nonattenuated MPSI patients . These cases were not from the Gifu MPSI pilot program, and repeat analyses for them are not available.…”

Section: Methodsmentioning

confidence: 99%

“…Mucopolysacharidosis type 1 (MPSI) (or Hurler syndrome, OMIM# 607014) has a variable age of onset, although early‐onset (ie, nonattenuated), severe phenotypes emerge in early infancy . Assays of the enzyme deficient in MPSI has been adapted to newborn blood spots . Treatment for MPSI is available through enzyme replacement therapy and stem cell transplantation …”

Section: Introductionmentioning

confidence: 99%

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Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

et al. 2020

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Purpose Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha‐L‐iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS). Methods We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early‐onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool. Results Every case of early‐onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early‐onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%. Conclusions Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis‐based approach, which was developed for Krabbe disease, can be extended to additional screened disorders.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

et al. 2020

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“…Blood and tissue GAG levels were measured by liquid chromatography-tandem mass spectrometry as described previously. [64][65][66][67][68] Briefly, 50 mM Tris-HCl (pH 7.0) and sample were added into a 96-well Omega 10K MWCO (molecular weight cutoff) filter plate (Pall Corporation, Port Washington, NY, USA) on a 96-well receiver plate. Samples were centrifuged for 15 min at 2,500 Â g. The filter plate was transferred to a new receiver plate, and a cocktail mixture of 50 mM Tris-HCl (pH 7.0), 5 mg/mL chondrosine as internal standard (IS), 1 mU heparitinase, and 1 mU keratanase II was added to the filter plate.…”

Section: Gag Assaymentioning

confidence: 99%

Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model

Sawamoto

Karumuthil‐Melethil

Khan

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Mucopolysaccharidosis type IVA (MPS IVA) is due to the deficiency of GALNS (N-acetylgalactosamine 6-sulfate sulfatase) and is characterized by systemic skeletal dysplasia. We have evaluated adeno-associated virus 8 (AAV8) vectors expressing different forms of human GALNS under a liver-specific promoter. The vectors were delivered intravenously into 4-weekold MPS IVA knockout (KO) and immune tolerant (MTOL) mice at a dose of 5 Â 10 13 genome copies (GC)/kg. These mice were monitored for 12 weeks post-injection. GALNS enzyme activity was elevated significantly in plasma of all treated mice at 2 weeks post-injection. The activity observed was 4-to 19-fold higher than that in wild-type mice and was maintained throughout the monitoring period. Treatment with AAV vectors resulted in a reduction of keratan sulfate (KS) levels in plasma to normal levels 2 weeks post-injection, which were maintained until necropsy. Both vectors reduced the storage in articular cartilage, ligaments, and meniscus surrounding articular cartilage and growth plate region as well as heart muscle and valves. Our results suggest that the continuous presence of high levels of circulating enzyme increases the penetration into bone and heart and reduces the KS level, thereby improving storage in these regions. The current data support a strategy for developing a novel treatment to address the bone and heart disease in MPS IVA using AAV gene therapy.

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Sweet but Challenging: Tackling the Complexity of GAGs with Engineered Tailor‐Made Biomaterials

Le Pennec,

Picart,

Vivès

et al. 2023

Advanced Materials

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Glycosaminoglycans (GAGs) play a crucial role in tissue homeostasis by regulating the activity and diffusion of bioactive molecules. Incorporating GAGs into biomaterials has emerged as a widely adopted strategy in medical applications, owing to their biocompatibility and ability to control the release of bioactive molecules. Nevertheless, immobilized GAGs on biomaterials can elicit distinct cellular responses compared to their soluble forms, underscoring the need to understand the interactions between GAG and bioactive molecules within engineered functional biomaterials. By controlling critical parameters such as GAG type, density, and sulfation, it becomes possible to precisely delineate GAG functions within a biomaterial context and to better mimic specific tissue properties, enabling tailored design of GAG‐based biomaterials for specific medical applications. However, this requires access to pure and well‐characterized GAG compounds, which remains challenging. This review focuses on different strategies for producing well‐defined GAGs and explores high‐throughput approaches employed to investigate GAG–growth factor interactions and to quantify cellular responses on GAG‐based biomaterials. These automated methods hold considerable promise for improving the understanding of the diverse functions of GAGs. In perspective, the scientific community is encouraged to adopt a rational approach in designing GAG‐based biomaterials, taking into account the in vivo properties of the targeted tissue for medical applications.

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Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

Cited by 4 publications

References 41 publications

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

Liver-Targeted AAV8 Gene Therapy Ameliorates Skeletal and Cardiovascular Pathology in a Mucopolysaccharidosis IVA Murine Model

Sweet but Challenging: Tackling the Complexity of GAGs with Engineered Tailor‐Made Biomaterials

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