Neonatal Screening for MPS Disorders in Latin America: A Survey of Pilot Initiatives

Kubaski, Francyne; Sousa, Inês; Amorim, Tatiana; Pereira, Danilo Florentino; Trometer, Joe; Souza, Alexandre Wagner Silva de; Ranieri, Enzo; Polo, Giulia; Burlina, Alberto; Brusius-Facchin, Ana Carolina; Netto, Alice Brinckmann Oliveira; Tomatsu, Shunji; Giugliani, Roberto

doi:10.3390/ijns6040090

Cited by 7 publications

(9 citation statements)

References 45 publications

(36 reference statements)

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“…Moreover, the dried blood spots (DBS) from 43 subjects with clinically suspected MPS or ML were analyzed, and both GAG and enzyme activity levels for MPS I, II, IIIB, IVA, and VI were analyzed. This paper extends the previous research on the validation of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for a five-plex assay for mucopolysaccharidoses [23][24][25][26][27][28][29][30][31].…”

Section: Introductionsupporting

confidence: 69%

“…,49d blood spots (DBS) from 43 subjects with clinically suspected MPS and both GAG and enzyme activity levels for MPS I, II, IIIB, IVA, . This paper extends the previous research on the validation of liqtandem mass spectrometry (LC-MS/MS) for a five-plex assay for es[23][24][25][26][27][28][29][30][31]. ods 43 patients with suspected MPS and 103 normal control subjects University, Shimane University, National Children's Hospital, and ese samples were stored at −20 °C.…”

mentioning

confidence: 63%

“…For this reason, it is critical to develop a newborn screening protocol and methodology of MPS that can be implemented in a statewide screening program. This newborn screening program can aid in the detection of disease before clinical signs and symptoms arise [18][19][20][21][22][23][24]. There are currently already over 20 states that have adopted newborn screening for MPS I [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

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Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

Arunkumar

Khan

et al. 2021

Diagnostics

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Mucopolysaccharidoses (MPS) and mucolipidosis (ML II/III) are a group of lysosomal storage disorders (LSDs) that occur due to a dysfunction of the lysosomal hydrolases responsible for the catabolism of glycosaminoglycans (GAGs). However, ML is caused by a deficiency of the enzyme uridine-diphosphate N-acetylglucosamine:lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. A timely diagnosis of MPS and ML can lead to appropriate therapeutic options for patients. To improve the accuracy of diagnosis for MPS and ML in a high-risk population, we propose a combination method based on known biomarkers, enzyme activities, and specific GAGs. We measured five lysosomal enzymes (α-L-iduronidase (MPS I), iduronate-2-sulfatase (MPS II), α-N-acetylglucosaminidase (MPS IIIB), N-acetylglucosamine-6-sulfatase (MPS IVA), and N-acetylglucosamine-4-sulfatase (MPS VI)) and five GAGs (two kinds of heparan sulfate (HS), dermatan sulfate (DS), and two kinds of keratan sulfate (KS)) in dried blood samples (DBS) to diagnose suspected MPS patients by five-plex enzyme and simultaneous five GAGs assays. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) for both assays. These combined assays were tested for 43 patients with suspected MPS and 103 normal control subjects. We diagnosed two MPS I, thirteen MPS II, one MPS IIIB, three MPS IVA, two MPS VI, and six ML patients with this combined method, where enzymes, GAGs, and clinical manifestations were compatible. The remaining 16 patients were not diagnosed with MPS or ML. The five-plex enzyme assay successfully identified MPS patients from controls. Patients with MPS I, MPS II, and MPS IIIB had significantly elevated HS and DS levels in DBS. Compared to age-matched controls, patients with ML and MPS had significantly elevated mono-sulfated KS and di-sulfated KS levels. The results indicated that the combination method could distinguish these affected patients with MPS or ML from healthy controls. Overall, this study has shown that this combined method is effective and can be implemented in larger populations, including newborn screening.

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Section: Introductionsupporting

confidence: 69%

mentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

Arunkumar

Khan

et al. 2021

Diagnostics

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“…The incidence of false positives in MPS screening is high, and secondary testing of newborns can eliminate some of the false positives. GAG testing in the same DBS can serve as a secondary test [ 14 ]; Kubaski, Sousa, et al [ 44 ]). In northeastern Italy, the introduction of a secondary test for GAG on the DBS resulted in a recall of MPS I from 0.05 to 0.006% [ 14 , 62 ].…”

Section: Biomarkersmentioning

confidence: 99%

Application of tandem mass spectrometry in the screening and diagnosis of mucopolysaccharidoses

Li,

Mao,

Chao

et al. 2024

Orphanet J Rare Dis

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Mucopolysaccharidoses (MPSs) are caused by a deficiency in the enzymes needed to degrade glycosaminoglycans (GAGs) in the lysosome. The storage of GAGs leads to the involvement of several systems and even to the death of the patient. In recent years, an increasing number of therapies have increased the treatment options available to patients. Early treatment is beneficial in improving the prognosis, but children with MPSs are often delayed in their diagnosis. Therefore, there is an urgent need to develop a method for early screening and diagnosis of the disease. Tandem mass spectrometry (MS/MS) is an analytical method that can detect multiple substrates or enzymes simultaneously. GAGs are reliable markers of MPSs. MS/MS can be used to screen children at an early stage of the disease, to improve prognosis by treating them before symptoms appear, to evaluate the effectiveness of treatment, and for metabolomic analysis or to find suitable biomarkers. In the future, MS/MS could be used to further identify suitable biomarkers for MPSs for early diagnosis and to detect efficacy.

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“…Newborn screening has become available for MPS, but only in a few countries (52,53) and it does not remain without flaws, such as false positives / negatives resulting in misdiagnosis (53). The limited availability and affordability of these tests remains a concern in developing countries.…”

Section: Early Diagnosismentioning

confidence: 99%

Unmet Cardiac Clinical Needs in Adult Mucopolysaccharidoses

Stępień

Braunlin

2022

Front. Cardiovasc. Med.

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The Mucopolysaccharidoses (MPSs) are a group of heterogenous disorders with complex multisystemic presentations. Although Haematopoietic Cell Transplantation (HCT) and Enzyme Replacement Therapy (ERT) have extended the lifespan of individuals affected with MPS well into adulthood, reversal of pre-existing cardiac, skeletal and neurocognitive deficits does not occur, so there are no truly curative treatments available to these patients at present. The medical and surgical management of cardiovascular problems in adults with MPS is complicated by these pre-existing comorbidities, requiring the involvement of multidisciplinary and multispecialty perioperative teams. This review sets out to describe the unmet cardiac needs in adults with MPS disorders including the lack of effective treatments, monitoring guidelines, and the challenges regarding expertise and training, and psychosocial support.

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Neonatal Screening for MPS Disorders in Latin America: A Survey of Pilot Initiatives

Cited by 7 publications

References 45 publications

Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

Application of tandem mass spectrometry in the screening and diagnosis of mucopolysaccharidoses

Unmet Cardiac Clinical Needs in Adult Mucopolysaccharidoses

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