Morquio‐like dysostosis multiplex presenting with neuronopathic features is a distinct GLB1‐related phenotype

Abstract

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.

Processed pseudogene insertion in GLB1 causes Morquio B disease by altering intronic splicing regulatory landscape

“…Clinically, MBD represents a relatively mild form of Morquio A disease, caused by the deficiency of another lysosomal enzyme—galactosamine 6-sulfatase ( GALNS ). The “pure MBD” manifests with progressive growth impairment and characteristic dysostosis multiplex, which generally includes three or more radiological/clinical findings: platyspondyly and vertebral beaking involving all segments of the spine, odontoid hypoplasia, epi- and metaphyseal dysplasia of long bones, genua/coxa valga, hip dysplasia, joint laxity/hyperextensible joints, barrel chest/pectus carinatum, and short stature 3 , 4 . Neuronopathic features can be presented in a small proportion of MBD patients, which can be classified by the “MBD plus” phenotype.…”

Morquio B disease: a case report

“…Similar to MBD patients described in the literature, this patient has been shown on MRI to have spinal canal and lumbar exit foramina narrowing with diffuse lumbar stenosis that are asymptomatic ( 10 , 12 ). While MBD patients such as the one described in this report are at risk for spinal cord compression, this is rarely reported in the literature ( 14 ).…”

GLB1-related disorders: GM1 gangliosidosis and Morquio B disease

“…Both diseases show a peculiar type of spondylo-epiphyseal dysplasia with or without additional neuronopathic manifestations. Despite these similarities, the degree of dysostosis multiplex is milder in Morquio B disease compared to MPS IVA [28][29][30]. The presence of keratan sulfate in the urine does not distinguish MPS IVA from Morquio B disease.…”