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

Abstract

Abstract Background Morquio‐B disease (MBD) is a distinct GLB1‐related dysostosis multiplex involving the trabecular parts of long bones and spine, presenting a mild phenocopy of GALNS‐related Morquio‐A disease. Methods We analyzed 63 (n = 62 published) cases with MBD to describe their clinical, biochemical and genetic features. Results Forty‐one of 51 cases with informative clinical data had pure MBD including progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly, odontoid hypoplasia. Ten of 51 had MBD plus neuronopathic manifestations including intellectual/developmental/speech delay, spasticity, ataxia dystonia. Corneal clouding, cardiac valve pathology, hepatosplenomegaly, spinal cord compression were infrequent and atlantooccipital dislocation, cardiomyopathy and cherry red spot were never reported. Urinary glycosaminoglycan and oligosaccharide excretion was consistently abnormal. Keratan sulphate‐derived oligosaccharides were only detected using LC‐MS/MS‐based methods. Residual β‐galactosidase activities measured against synthetic substrates were 0%‐17%. Among 28 GLB1 variants, W273 L (34/94 alleles) and T500A (11/94 alleles) occurred most frequently. W273L was invariably associated with pure MBD. Pure MBD also was reported in a case homozygous for R201H, and in the majority of cases carrying the T500A variant. Homozygous Y333C and G438E were associated with MBD plus neuronopathic manifestations. T82M, R201H, and H281Y, observed in seven alleles, previously have been found sensitive to experimental chaperones. Conclusion Data provide a basis for future systematic collection of clinical, biochemical, morphologic, and genetic data of this ultra‐rare condition.

Keywords

• dwarfism
• literature review
• mucopolysaccharidosis
• natural history
• spondyloepiphyseal dysplasia