Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII

Kubaski, Francyne; Brusius-Facchin, Ana Carolina; Mason, Robert W.; Patel, Pravin; Burin, Maira G.; Michelin‐Tirelli, Kristiane; Kessler, Rejane Gus; Bender, Fernanda; Leistner-Segal, Sandra; Moreno, Carolina; Cavalcanti, Denise Pontes; Giugliani, Roberto; Tomatsu, Shunji

doi:10.1002/pd.5028

Cited by 22 publications

(15 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The early identification of MPS affected newborns remains challenging since most of them do not exhibit any signs of the disease early in life [23]. However, considering that several studies demonstrated that GAGs are elevated as early as 21 weeks of gestation [9,24], we strongly believe that newborn screening will be a useful tool to identify patients before the onset of irreversible signs and symptoms associated with the disease. We described herein, the development and validation of a UPLC-MS/MS multiplex method, which allows an absolute quantification of HS, DS and creatinine, and is suitable for newborn screening of MPS I, II, III, VI, and VII using urine DUS from 21-day-old newborns.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Mass Urine Screening Approach for Early Detection of Mucopolysaccharidoses by UPLC-MS/MS

et al. 2019

View full text Add to dashboard Cite

Mucopolysaccharidoses (MPSs) are lysosomal storage disorders caused by deficiencies of enzymes involved in the catabolism of glycosaminoglycans (GAGs). Various treatments such as enzyme replacement therapy and/or hematopoietic stem cell transplant are available for MPSs. Early initiation of treatment improves the outcome and delays the onset of symptoms, highlighting the need for newborn screening for MPSs. The main objective of this project was to devise and validate a multiplex urine filter paper method for GAG analysis using a tandem mass spectrometry (MS/MS) approach to screen newborns for MPSs. Eluted urine samples from 21-day-old newborns were evaporated and a methanolysis reaction was performed. Samples were resuspended and analyzed using a UPLC-MS/MS system. A one-minute chromatographic method allowed the absolute quantification of heparan sulfate (HS), dermatan sulfate (DS), and creatinine. Method validation revealed high precision (< 9% relative standard deviation) and accuracy (< 7% bias) for all analytes. The reference values normalized to creatinine obtained by the analysis of five hundred 21-day-old newborn urine samples were 34.6 +/-6.2 mg/mmol of creatinine and 17.3 +/-3.9 mg/mmol of creatinine for HS and DS, respectively. We present a rapid and efficient method for populational newborn urine screening using MS/MS, which could also be applied to high-risk screening.

show abstract

Section: Discussionmentioning

confidence: 99%

Neonatal Mass Urine Screening Approach for Early Detection of Mucopolysaccharidoses by UPLC-MS/MS

et al. 2019

View full text Add to dashboard Cite

show abstract

“…To quantify GAGs in different matrices, liquid chromatography tandem mass spectrometry has been used [48]. GAGs can be quantified in: urine [34,[49][50][51][52][53][54], serum/plasma [34,48,[54][55][56], dried blood spots [57][58][59] (Figure 3), amniotic fluid [60], cerebrospinal fluid [34,61], cultured cells [34], and tissues [62]. Some of these assays can be used for newborn screening of MPSs [57,63] or even to allow the discrimination of specific disease subtypes [53].…”

Section: Biomarkersmentioning

confidence: 99%

Diagnosis of Mucopolysaccharidoses

et al. 2020

Self Cite

View full text Add to dashboard Cite

The mucopolysaccharidoses (MPSs) include 11 different conditions caused by specific enzyme deficiencies in the degradation pathway of glycosaminoglycans (GAGs). Although most MPS types present increased levels of GAGs in tissues, including blood and urine, diagnosis is challenging as specific enzyme assays are needed for the correct diagnosis. Enzyme assays are usually performed in blood, with some samples (as leukocytes) providing a final diagnosis, while others (such as dried blood spots) still being considered as screening methods. The identification of variants in the specific genes that encode each MPS-related enzyme is helpful for diagnosis confirmation (when needed), carrier detection, genetic counseling, prenatal diagnosis (preferably in combination with enzyme assays) and phenotype prediction. Although the usual diagnostic flow in high-risk patients starts with the measurement of urinary GAGs, it continues with specific enzyme assays and is completed with mutation identification; there is a growing trend to have genotype-based investigations performed at the beginning of the investigation. In such cases, confirmation of pathogenicity of the variants identified should be confirmed by measurement of enzyme activity and/or identification and/or quantification of GAG species. As there is a growing number of countries performing newborn screening for MPS diseases, the investigation of a low enzyme activity by the measurement of GAG species concentration and identification of gene mutations in the same DBS sample is recommended before the suspicion of MPS is taken to the family. With specific therapies already available for most MPS patients, and with clinical trials in progress for many conditions, the specific diagnosis of MPS as early as possible is becoming increasingly necessary. In this review, we describe traditional and the most up to date diagnostic methods for mucopolysaccharidoses.

show abstract

“…β-glucuronidase is an essential lysosomal enzyme that participates in the later steps of the catabolism of multiple species of GAG polysaccharides and proteoglycans. Recessively inherited loss-of-function mutations in GUSB causes the mucopolysaccharidosis Sly's syndrome (MPS VII) (Heuer et al, 2001;Kubaski et al, 2017;Kyle et al, 1990;Paigen, 1989;Ray et al, 1999;Zielonka et al, 2017). Prior ChIPseq data from human K562 cells demonstrates that THAP1 is bound to the GUSB promoter ( Fig.…”

Section: Thap1 Binds To and Regulates The Gusb (Mps Vii) Gene Encodinmentioning

confidence: 99%

THAP1 Modulates Oligodendrocyte Maturation by Regulating ECM Degradation in Lysosomes

Yellajoshyula

Pappas

Rogers

et al. 2020

Preprint

View full text Add to dashboard Cite

Mechanisms controlling myelination during CNS maturation play a pivotal role in the development and refinement of CNS circuits. The transcription factor THAP1 is essential for timing the inception of myelination during CNS maturation through a cell-autonomous role in the oligodendrocyte lineage. Here, we demonstrate that THAP1 modulates ECM composition by regulating glycosaminoglycan (GAG) catabolism within oligodendrocyte progenitor cells (OPCs). Thap1-/- OPCs accumulate and secrete excess GAGs, inhibiting their maturation through an auto-inhibitory mechanism. THAP1 controls GAG metabolism by binding to and regulating the GusB gene encoding β-glucuronidase, a GAG-catabolic lysosomal enzyme. Applying GAG-degrading enzymes or overexpressing β-glucuronidase rescues Thap1-/- OL maturation deficits in vitro and in vivo. Our studies establish lysosomal GAG catabolism within OPCs as a critical mechanism regulating oligodendrocyte development.

show abstract

Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII

Cited by 22 publications

References 56 publications

Neonatal Mass Urine Screening Approach for Early Detection of Mucopolysaccharidoses by UPLC-MS/MS

Neonatal Mass Urine Screening Approach for Early Detection of Mucopolysaccharidoses by UPLC-MS/MS

Diagnosis of Mucopolysaccharidoses

THAP1 Modulates Oligodendrocyte Maturation by Regulating ECM Degradation in Lysosomes

Contact Info

Product

Resources

About