Estimated birth prevalence of mucopolysaccharidoses in Brazil

Federhen, Andressa; Pasqualim, Gabriela; Freitas, Talita Freitas de; Gonzalez, Esteban Alberto; Trapp, Franciele Barbosa; Matte, Úrsula; Giugliani, Roberto

doi:10.1002/ajmg.a.61456

Cited by 22 publications

(23 citation statements)

References 42 publications

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“…This means that we may have overestimated the prevalence of diseases in the general population. A recent study estimated the prevalence of MPS in Brazil based on 600 affected individuals with all types of MPS included in a national network database [ 21 ]. The researchers found discrepancy when comparing the estimated prevalence based on diagnosis (0.24/100,000) to the estimated prevalence based on genetic screening for the most common pathogenic variant in IDUA among healthy volunteers (0.95/100,000), for example.…”

Section: Discussionmentioning

confidence: 99%

Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes

Borges

Pasqualim

Giugliani

et al. 2020

Orphanet J Rare Dis

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Background In this study, the prevalence of different types of mucopolysaccharidoses (MPS) was estimated based on data from the exome aggregation consortium (ExAC) and the genome aggregation database (gnomAD). The population-based allele frequencies were used to identify potential disease-causing variants on each gene related to MPS I to IX (except MPS II). Methods We evaluated the canonical transcripts and excluded homozygous, intronic, 3′, and 5′ UTR variants. Frameshift and in-frame insertions and deletions were evaluated using the SIFT Indel tool. Splice variants were evaluated using SpliceAI and Human Splice Finder 3.0 (HSF). Loss-of-function single nucleotide variants in coding regions were classified as potentially pathogenic, while synonymous variants outside the exon–intron boundaries were deemed non-pathogenic. Missense variants were evaluated by five in silico prediction tools, and only those predicted to be damaging by at least three different algorithms were considered disease-causing. Results The combined frequencies of selected variants (ranged from 127 in GNS to 259 in IDUA) were used to calculate prevalence based on Hardy–Weinberg's equilibrium. The maximum estimated prevalence ranged from 0.46 per 100,000 for MPSIIID to 7.1 per 100,000 for MPS I. Overall, the estimated prevalence of all types of MPS was higher than what has been published in the literature. This difference may be due to misdiagnoses and/or underdiagnoses, especially of the attenuated forms of MPS. However, overestimation of the number of disease-causing variants by in silico predictors cannot be ruled out. Even so, the disease prevalences are similar to those reported in diagnosis-based prevalence studies. Conclusion We report on an approach to estimate the prevalence of different types of MPS based on publicly available population-based genomic data, which may help health systems to be better prepared to deal with these conditions and provide support to initiatives on diagnosis and management of MPS.

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Section: Discussionmentioning

confidence: 99%

Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes

Borges

Pasqualim

Giugliani

et al. 2020

Orphanet J Rare Dis

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“…The evaluation of GAG levels will provide a diagnostic and prognostic biomarker to predict the course of the disease. Each type of MPS has a broad range of clinical manifestations [ 5 , 6 ]. Early recognition of MPS remains an unmet challenge since the clinical phenotype looks normal at birth.…”

Section: Introductionmentioning

confidence: 99%

“…Early recognition of MPS remains an unmet challenge since the clinical phenotype looks normal at birth. Thus, recognizing MPS remains unnoticed in most patients until the disease has progressed and is prominent [ 6 , 7 , 8 ]. Early diagnosis of the disease provides more therapeutic options and proper management for the patients [ 7 , 9 ] that provides a better quality of life and slows or prevents irreversible damage [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of Mucopolysaccharidoses Update

Çelik

Tomatsu

et al. 2021

Diagnostics

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Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a lysosomal enzyme deficiency or malfunction, which leads to the accumulation of glycosaminoglycans in tissues and organs. If not treated at an early stage, patients have various health problems, affecting their quality of life and life-span. Two therapeutic options for MPS are widely used in practice: enzyme replacement therapy and hematopoietic stem cell transplantation. However, early diagnosis of MPS is crucial, as treatment may be too late to reverse or ameliorate the disease progress. It has been noted that the prevalence of MPS and each subtype varies based on geographic regions and/or ethnic background. Each type of MPS is caused by a wide range of the mutational spectrum, mainly missense mutations. Some mutations were derived from the common founder effect. In the previous study, Khan et al. 2018 have reported the epidemiology of MPS from 22 countries and 16 regions. In this study, we aimed to update the prevalence of MPS across the world. We have collected and investigated 189 publications related to the prevalence of MPS via PubMed as of December 2020. In total, data from 33 countries and 23 regions were compiled and analyzed. Saudi Arabia provided the highest frequency of overall MPS because of regional or consanguineous marriages (or founder effect), followed by Portugal, Brazil, the Netherlands, and Australia. The newborn screening is an efficient and early diagnosis for MPS. MPS I has been approved for newborn screening in the United States. After the newborn screening of MPS I, the frequency of MPS I increased, compared with the past incidence rates. Overall, we conclude that the current identification methods are not enough to recognize all MPS patients, leading to an inaccurate incidence and status. Differences in ethnic background and/or founder effects impact on the frequency of MPS, which affects the prevalence of MPS. Two-tier newborn screening has accelerated early recognition of MPS I, providing an accurate incidence of patients.

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“…More than 30% of patients affected with lysosomal diseases have mucopolysaccharidoses (MPS), disorders affecting the enzymes involved in the stepwise degradation of glycosaminoglycans (GAGs) [1][2][3][4]. Seven MPS are caused by genetic deficiencies in enzymes participating in heparan sulfate (HS) catabolism.…”

Section: Introductionmentioning

confidence: 99%

Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms

Viana

Priestman

Platt

et al. 2020

JCM

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Mucopolysaccharidoses (MPS) are the group of lysosomal storage disorders caused by deficiencies of enzymes involved in the stepwise degradation of glycosaminoglycans. To identify brain pathology common for neurological MPS, we conducted a comprehensive analysis of brain cortex tissues from post-mortem autopsy materials of eight patients affected with MPS I, II, IIIA, IIIC, and IIID, and age-matched controls. Frozen brain tissues were analyzed for the abundance of glycosaminoglycans (heparan, dermatan, and keratan sulfates) by LC-MS/MS, glycosphingolipids by normal phase HPLC, and presence of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor superfamily member 10 (TNFSF10) by Western blotting. Fixed tissues were stained for the markers for microgliosis, astrogliosis, misfolded proteins, impaired autophagy, and GM2 ganglioside. Our results demonstrate that increase of heparan sulfate, decrease of keratan sulfate, and storage of simple monosialogangliosides 2 and 3 (GM2 and GM3) as well as the neutral glycosphingolipid, LacCer, together with neuroinflammation and neuronal accumulation of misfolded proteins are the hallmarks of brain pathology in MPS patients. These biomarkers are similar to those reported in the corresponding mouse models, suggesting that the pathological mechanism is common for all neurological MPS in humans and mice.

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Estimated birth prevalence of mucopolysaccharidoses in Brazil

Cited by 22 publications

References 42 publications

Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes

Estimated prevalence of mucopolysaccharidoses from population-based exomes and genomes

Epidemiology of Mucopolysaccharidoses Update

Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms

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