학술논문
Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype
Document Type
Report
Author
Stockler‐Ipsiroglu, Sylvia; Yazdanpanah, Nahid; Yazdanpanah, Mojgan; Popurs, Marioara Moisa; Yuskiv, Nataliya; Santos, Mara Lúcia Schmitz Ferreira; Kim, Chong Ae; De Souza, Carolina Fischinger Moura; Lourenço, Charles Marques; Steiner, Carlos Eduardo; Federhen, Andressa; Giugliani, Luciana; Pereira, Débora Maria Bastos; Durán‐Carabali, Luz Elena; Giugliani, Roberto
Source
JIMD Reports. July 2021, Vol. 60 Issue 1, p23, 9 p.
Subject
Language
English
Abstract
INTRODUCTION Morquio B disease (MBD), also called mucopolysaccharidosis IVB (OMIM # 253010), is a rare lysosomal storage disorder, which is allelic to GM1‐gangliosidosis (OMIM # 230500). Both MBD and GM1‐gangliosidosis [...]
: Background: Morquio B disease (MBD) is a distinct GLB1‐related dysostosis multiplex presenting a mild phenocopy of GALNS‐related Morquio A disease. Previously reported cases from European countries carry the W273L variant on at least one GLB1 allele and exhibit a pure skeletal phenotype (pure MBD). Only a minority of MBD cases have been described with additional neuronopathic findings (MBD plus). Objectives and Methods: With the aim to further describe patterns of MBD‐related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with GLB1‐related dysostosis multiplex living and diagnosed in Brazil. Results: About 14 of the 17 individuals had three or more skeletal findings characteristic of Morquio syndrome. Two had no additional neuronopathic features (pure MBD) and 12 exhibited additional neuronopathic features (MBD plus). Three of the 17 cases had mild dysostosis without distinct features of MBD. Seven of the 12 MBD plus patients had signs of spinal cord compression (SCC), as a result of progressive spinal vertebral dysostosis. There was an age‐dependent increase in the number of skeletal findings and in the severity of growth impairment. GLB1 mutation analysis was completed in 10 of the 14 MBD patients. T500A occurred in compound heterozygosity in 8 of the 19 alleles. Conclusion: Our study extends the phenotypic spectrum of GLB1‐related conditions by describing a cohort of patients with MBD and GM1‐gangliosidosis (MBD plus). Targeting the progressive nature of the skeletal manifestations in the development of new therapies for GLB1‐related conditions is warranted.
: Background: Morquio B disease (MBD) is a distinct GLB1‐related dysostosis multiplex presenting a mild phenocopy of GALNS‐related Morquio A disease. Previously reported cases from European countries carry the W273L variant on at least one GLB1 allele and exhibit a pure skeletal phenotype (pure MBD). Only a minority of MBD cases have been described with additional neuronopathic findings (MBD plus). Objectives and Methods: With the aim to further describe patterns of MBD‐related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with GLB1‐related dysostosis multiplex living and diagnosed in Brazil. Results: About 14 of the 17 individuals had three or more skeletal findings characteristic of Morquio syndrome. Two had no additional neuronopathic features (pure MBD) and 12 exhibited additional neuronopathic features (MBD plus). Three of the 17 cases had mild dysostosis without distinct features of MBD. Seven of the 12 MBD plus patients had signs of spinal cord compression (SCC), as a result of progressive spinal vertebral dysostosis. There was an age‐dependent increase in the number of skeletal findings and in the severity of growth impairment. GLB1 mutation analysis was completed in 10 of the 14 MBD patients. T500A occurred in compound heterozygosity in 8 of the 19 alleles. Conclusion: Our study extends the phenotypic spectrum of GLB1‐related conditions by describing a cohort of patients with MBD and GM1‐gangliosidosis (MBD plus). Targeting the progressive nature of the skeletal manifestations in the development of new therapies for GLB1‐related conditions is warranted.