MPS IV

Morquio syndrome is a lysosomal storage disease caused by defects in one of two enzymes involved in the degradation of keratan sulphate.

The clinical picture is of normal intelligence but severe dysostosis.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome, OMIM 253000) is an autosomal recessive lysosomal storage disorder (LSD) that was first described by Luis Morquio and James Brailsford in 1929

• caused by a deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, which leads to a progressive accumulation of the glycosaminoglycans (GAGs) chondroitin-6-sulfate (C6S) and keratan sulfate (KS)
  • accumulation of undegraded C6S and KS triggers progressive systemic skeletal dysplasia in MPS IVA patients
  • MPS IVA is more frequently associated with severe and extensive skeletal manifestations than the other MPS types
    • hypermobility of the joints is a characteristic of MPS IVA that distinguishes this disease from the other types
    • these patients exhibit no cognitive involvement

Natural history:

• in the mild form, the symptoms can appear as late as the second decade of life, and some patients can reach a normal stature
• patients with a severe form of MPS IVA may not survive beyond the second or third decade of life (1)

Management:

• enzyme replacement therapy (ERT) with elosulfase alfa (recombinant human GALNS)
• NICE state:
  • elosulfase alfa is recommended, within its marketing authorisation, as an option for treating mucopolysaccharidosis type 4A (MPS 4A) for people of all ages

Reference:

• Pintos-Morell G, Blasco-Alonso J, Couce ML, et al. Elosulfase alfa for mucopolysaccharidosis type IVA: Real-world experience in 7 patients from the Spanish Morquio-A early access program. Mol Genet Metab Rep. 2018;15:116-120. Published 2018 Apr 5. doi:10.1016/j.ymgmr.2018.03.009
• NICE (April 2022). Elosulfase alfa for treating mucopolysaccharidosis type 4A