Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

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- and 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- and 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. Electronic supplementary material The online version of this article (10.1186/s13023-019-1074-9) contains supplementary material, which is available to authorized users.

Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings

“…Until now, there has been no proof that ERT has an impact on bone lesions. Still, according to Akyol et al [29], the data are mainly limited to ERT among patients who initiated ERT relatively late into their disease progression. The limited data may cause reimbursement companies and physicians to not support ERT in relatively young children [30].…”

Critical clinical situations in adult patients with Mucopolysaccharidoses (MPS)

“…Due to intubation during surgery and the accompanying soft tissue manipulation, patients may also be at risk of oedema of the airways. As this is frequently coupled with other respiratory features of MPS, post-surgical observation in an intensive care unit is a key stage of the initial recovery period (32,33), and a place in such a unit should be available for all MPS patients in the 24 hours following surgery. Feeding plans need to adapt as the patient recovers, and individualised physiotherapy requirements should be in place to support the patient's rehabilitation (Supplementary information: Post-surgical care).…”

“…For the first 4 weeks post-surgery, it is recommended that ERT infusions are not provided, which is due to several key factors. First, the risk of anaphylactic reactions to ERT during sepsis or fever is higher; recommendations for MPS IVA, and safety information for ERT for MPS I state that infusions should be avoided in this acute post-surgical setting as patients may experience sepsis or fever during recovery (32,39). Second, adverse events associated with ERT can include fever and chills (14,32,33), and if ERT were provided soon after surgery, determining the cause of such symptoms as ERT-related or surgery-related would be challenging, leading to difficulties in managing the symptom.…”

“…For example, difficult intubations because of narrowed airways are major factors in deferring complex surgeries(47).Intubation difficulties are estimated to occur in 25% of patients with MPS, so the MDT may wish to take additional steps prior to this procedure to be fully prepared if initial procedures do not go ahead as expected. It should be emphasised that recommendations state that surgical procedures should be carried out by, or under the guidance of, MPS experts in centres with intensive care units, and some clinicians will have to assess if they have the necessary expertise and facilities at their centre to manage the challenges of surgery in patients with MPS(32,33).Coordination of MPS care is particularly important as patients with MPS are at high risk of surgical complications and knowledge of these is the key to optimising each procedure(4,5,21,22). A metabolic specialist should also be involved in decision-making with regard to the potential benefits and risks of surgery.…”

Surgical Management of Spinal Disorders in People with Mucopolysaccharidoses

“…Establishing appropriate surgical indications for spinal disorders in MPS remains a challenge though guidelines of MPS have recently been launched [63,64]. Despite new therapeutic modalities such as ERT/HSCT, which are expected to contribute prolonging the life expectancy of patients with MPS, problems remain regarding musculoskeletal disorders, especially spinal problems.…”