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

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

Morquio B patient/caregiver survey: First insight into the natural course of a rare GLB1 related condition

Morquio B disease (MBD) or Mucopolysaccharidosis type IV B (MPS IV B) is caused by particular GLB1 mutations specifically affecting the affinity of beta-galactosidase to keratan sulphate, resulting in dysostosis multiplex resembling Morquio A (MPS IV A) disease (GALNS deficiency). Additional neuronopathic features of GM1 II/III (juvenile/adult) gangliosidosis have been reported in some patients. Our patient/caregiver online survey was aimed at elucidating the clinical manifestations of this ultra-rare condition.Comparing to previously published data on MPS IV A, the 30 respondents in our MBD group presented with greater growth chart values (weight and height) and with lesser effects of odontoid hypoplasia. The most common concerns are: (1) mobility issues - 84% having difficulty walking; (2) chronic pain - 96%; (3) surgeries - average 3 per person, 80% for hip problems; (4) hip dysplasia, knee/ankle concerns, and scoliosis. Approximately 50% of MBD participants live independently and actively contributing to society.Evidence from our survey results supports the notion that skeletal manifestations in MBD are milder than in the majority of patients with MPS IV A. The data collected will help with the establishment of clinically meaningful outcomes for future therapeutic trials, and with the counseling of newly diagnosed patients about their health expectations. Keywords: Skeletal dysplasia, GM1 gangliosidosis, Lysosome, Natural histor