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

Abstract

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.

Morquio‐B disease: Clinical and genetic characteristics of a distinct GLB1‐related dysostosis multiplex

“…Results also have reinforced the general understanding that the skeletal manifestations are mild in MBD when compared to typical Morquio‐A disease and clinically indistinguishable from mild Morquio‐A variants . Along with this notion, we previously could show that the height of adult MBD patients is significantly less compromised than of those with typical Morquio‐A disease . Notably, three of the five adults (24‐39 years old) depicted in Table had only a mildly impaired body height (minus 1.2 SD‐minus 2 SD).…”

“…Apart from a single study in a skin biopsy of a patient with MBD, biochemical and morphologic studies on extracellular matrix or bone pathology have not been performed for MBD. Future studies similar to those performed for numerous other LSDs and for Morquio‐A disease may serve for a better understanding of the clinical differences between Morquio‐A disease and MBD (eg, why surgical operations in MBD patients differ significantly from those with Morquio‐A disease both in regards to the types of intervention, and in regards to the age at which these surgeries become necessary …”

“…39,42,43 Along with this notion, we previously could show that the height of adult MBD patients is significantly less compromised than of those with typical Morquio-A disease. 44 Notably, three of the five adults (24-39 years old) depicted in Table 3 had only a mildly impaired body height (minus 1.2 SD-minus 2 SD). Conversely, among the six individuals younger than 6 years, only the patient reported by Sheth et al 29 had early onset dwarfism with a body height at minus 3.8 SD at the age of 3 years.…”

“…Future studies similar to those performed for numerous other LSDs 51 and for Morquio-A disease 52,53 may serve for a better understanding of the clinical differences between Morquio-A disease and MBD (eg, why surgical operations in MBD patients differ significantly from those with Morquio-A disease both in regards to the types of intervention, and in regards to the age at which these surgeries become necessary. 44 Neuronopathic manifestations in MBD span from an early onset global developmental delay with delayed achievement of motor milestones, speech delay to intellectual disability, progressive spasticity, and dystonia (CV 1). Onset of neurocognitive deficiencies can be later in life (CV 2), with skeletal findings being the first red flag (CV 3).…”

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

“…However, while GALNS ‐related Morquio A and GLB1 ‐related MBD share similar patterns of dysostosis multiplex, skeletal manifestations are usually milder in MBD when compared to typical Morquio‐A disease. Along with this notion, we previously could show that the height of adult MBD patients is significantly less compromised than that of those with typical Morquio A disease 5 …”