Diagnosis of Mucopolysaccharidoses
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-03-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/10/3/172 |
| _version_ | 1828117592420646912 |
|---|---|
| author | Francyne Kubaski Fabiano de Oliveira Poswar Kristiane Michelin-Tirelli Maira Graeff Burin Diana Rojas-Málaga Ana Carolina Brusius-Facchin Sandra Leistner-Segal Roberto Giugliani |
| author_facet | Francyne Kubaski Fabiano de Oliveira Poswar Kristiane Michelin-Tirelli Maira Graeff Burin Diana Rojas-Málaga Ana Carolina Brusius-Facchin Sandra Leistner-Segal Roberto Giugliani |
| author_sort | Francyne Kubaski |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:17:54Z |
| format | Article |
| id | doaj.art-3804d55249a24e30aba0f28877fac8c2 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-04-11T13:17:54Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-3804d55249a24e30aba0f28877fac8c22022-12-22T04:22:20ZengMDPI AGDiagnostics2075-44182020-03-0110317210.3390/diagnostics10030172diagnostics10030172Diagnosis of MucopolysaccharidosesFrancyne Kubaski0Fabiano de Oliveira Poswar1Kristiane Michelin-Tirelli2Maira Graeff Burin3Diana Rojas-Málaga4Ana Carolina Brusius-Facchin5Sandra Leistner-Segal6Roberto Giugliani7Postgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre 91501-970, BrazilPostgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre 91501-970, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilPostgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre 91501-970, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilMedical Genetics Service, HCPA, Porto Alegre 90035-903, BrazilPostgraduate Program in Genetics and Molecular Biology, UFRGS, Porto Alegre 91501-970, BrazilThe 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.https://www.mdpi.com/2075-4418/10/3/172mucopolysaccharidosesglycosaminoglycansenzyme replacement therapytandem mass spectrometrynewborn screening. |
| spellingShingle | Francyne Kubaski Fabiano de Oliveira Poswar Kristiane Michelin-Tirelli Maira Graeff Burin Diana Rojas-Málaga Ana Carolina Brusius-Facchin Sandra Leistner-Segal Roberto Giugliani Diagnosis of Mucopolysaccharidoses Diagnostics mucopolysaccharidoses glycosaminoglycans enzyme replacement therapy tandem mass spectrometry newborn screening. |
| title | Diagnosis of Mucopolysaccharidoses |
| title_full | Diagnosis of Mucopolysaccharidoses |
| title_fullStr | Diagnosis of Mucopolysaccharidoses |
| title_full_unstemmed | Diagnosis of Mucopolysaccharidoses |
| title_short | Diagnosis of Mucopolysaccharidoses |
| title_sort | diagnosis of mucopolysaccharidoses |
| topic | mucopolysaccharidoses glycosaminoglycans enzyme replacement therapy tandem mass spectrometry newborn screening. |
| url | https://www.mdpi.com/2075-4418/10/3/172 |
| work_keys_str_mv | AT francynekubaski diagnosisofmucopolysaccharidoses AT fabianodeoliveiraposwar diagnosisofmucopolysaccharidoses AT kristianemichelintirelli diagnosisofmucopolysaccharidoses AT mairagraeffburin diagnosisofmucopolysaccharidoses AT dianarojasmalaga diagnosisofmucopolysaccharidoses AT anacarolinabrusiusfacchin diagnosisofmucopolysaccharidoses AT sandraleistnersegal diagnosisofmucopolysaccharidoses AT robertogiugliani diagnosisofmucopolysaccharidoses |