Morquio B disease: From pathophysiology towards diagnosis.
Mol Genet Metab
; 132(3): 180-188, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33558080
ABSTRACT
Morquio B disease is an attenuated phenotype within the spectrum of beta galactosidase (GLB1) deficiencies. It is characterised by dysostosis multiplex, ligament laxity, mildly coarse facies and heart valve defects due to keratan sulphate accumulation, predominantly in the cartilage. Morquio B patients have normal neurological development, setting them apart from those with the more severe GM1 gangliosidosis. Morquio B disease, with an incidence of 1250.000 to 11.000.000 live births, is very rare. Here we report the clinical-biochemical data of nine patients. High amounts of keratan sulfate were detected using LC-MS/MS in the patients' urinary samples, while electrophoresis, the standard procedure of qualitative glycosaminoglycans analysis, failed to identify this metabolite in any of the patients' samples. We performed molecular analyses at gene, gene expression and protein expression levels, for both isoforms of the GLB1 gene, lysosomal GLB1, and the cell-surface expressed Elastin Binding Protein. We characterised three novel GLB1 mutations [c.75 + 2 T > G, c.575A > G (p.Tyr192Cys) and c.2030 T > G (p.Val677Gly)] identified in three heterozygous patients. We also set up a copy number variation assay by quantitative PCR to evaluate the presence of deletions/ insertions in the GLB1 gene. We propose a diagnostic plan, setting out the specific clinical- biochemical and molecular features of Morquio B, in order to avoid misdiagnoses and improve patients' management.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gangliosidose GM1
/
Beta-Galactosidase
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Mucopolissacaridose IV
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Glicosaminoglicanos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Qualitative_research
Limite:
Child
/
Child, preschool
/
Female
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Humans
/
Male
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália