Recommendations for the management of MPS IVA: Systematic evidence- A nd consensus-based guidance

Mehmet Umut Akyol, Tord D. Alden, Hernan Amartino, Jane Ashworth, Kumar Belani, Kenneth I. Berger, Andrea Borgo, Elizabeth Braunlin, Yoshikatsu Eto, Jeffrey I. Gold, Andrea Jester, Simon A. Jones, Cengiz Karsli, William Mackenzie, Diane Ruschel Marinho, Andrew McFadyen, Jim McGill, John J. Mitchell, Joseph Muenzer, Torayuki OkuyamaPaul J. Orchard, Bob Stevens, Sophie Thomas, Robert Walker, Robert Wynn, Roberto Giugliani, Paul Harmatz, Christian Hendriksz*, Maurizio Scarpa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Introduction: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA. Methods: Twenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. Results: A total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). Conclusion: This manuscript provides evidence- A nd consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- A nd patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

Original languageEnglish (US)
Article number137
JournalOrphanet journal of rare diseases
Volume14
Issue number1
DOIs
StatePublished - Jun 13 2019

Keywords

  • Anaesthetics
  • ERT
  • Elosulfase alfa
  • Enzyme replacement therapy
  • HSCT
  • Haematopoietic stem cell transplantation
  • MPS IVA
  • Management guidelines
  • Morquio a syndrome
  • Mucopolysaccharidosis
  • Surgery
  • VIMIZIM

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

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