Morquio-B disease: Clinical and genetic characteristics of a distinct -related dysostosis multiplex.

BACKGROUND

Morquio-B disease (MBD) is a distinct -related dysostosis multiplex involving the trabecular parts of long bones and spine, presenting a mild phenocopy of -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 including progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly, odontoid hypoplasia. Ten of 51 had 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 variants, W273 L (34/94 alleles) and T500A (11/94 alleles) occurred most frequently. W273L was invariably associated with . 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 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.