Dynamic Gait Analysis in Children With Mucopolysaccharidosis Type IVa

Mucopolysaccharidosis Type IVa (MPS IVa, Morquio Disease) is a rare inherited lysosomal storage disorder caused by deficiency of the enzyme galactose-6-sulfatase.

Children with this disease accumulate a chemical called keratan sulphate, which stops their skeletons developing properly. They are very short in stature and many of their joints are unstable. Children with MPS IVa walk in a different way to other people due to a combination of lax ligaments and skeletal problems such as knock-knees.

Human walking involves the coordinated movements of all four limbs. As we walk, the arms swing oppositely to the legs. This movement pattern is very different in children with MPS IVa. This change seems to involve the whole musculoskeletal system and depends on the severity of the disease.

Recent studies in children with MPS IVa describing walking pattern have concentrated solely on the lower or upper limb respectively, and have not looked at the interaction of the upper and lower limbs during walking.

To our knowledge, the mechanics of walking in children with MPS IVa has not been investigated using a dynamic gait analysis tool (using cameras, sensors and electrodes to track the movements of different parts of the body during walking) and we aim to characterise this in a small number of children with MPS IVa and also examine the effects of splinting the wrist upon the walking pattern to see if this simple intervention makes it easier or more difficult for children with MPS IVa to walk.

Study Overview

• Status: Withdrawn
• Conditions: Mucopolysaccharidosis IV; Morquio A Disease

• Study Type: Observational

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Children's Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children With Mucopolysaccharidosis Type IVa

Description

Inclusion Criteria:

• Confirmed diagnosis of MPS IVa (documented history of reduced leucocyte GALNS enzyme activity relative to the normal range of the laboratory performing the assay AND/OR molecular analysis showing two pathogenic mutations in the GALNS gene)
• Willing and able to provide written assent and parent/legal guardian able to provide written informed consent after the nature of the study has been explained and prior to any research-related procedures
• Between 6 and 18 years of age inclusive
• Willing to perform all study procedures as far as physically possible

Exclusion Criteria:

• Inability to comply with Gait Analysis protocol (e.g. nonambulant)
• Recent orthopaedic surgery that investigator deems might impact on Gait Analysis
• Use of any investigational product or investigational medical device other than BMN110 within 30 days prior to recruitment, or requirement for any investigational agent other than BMN110 prior to completion of all scheduled study assessments
• Concurrent disease or condition that would interfere with study participation or safety
• Any condition that, in the view of the Principal or Subinvestigators, places the subject at high risk of not completing the study procedures

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Children With Mucopolysaccharidosis Type IVa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evidence of abnormal walking pattern and surface EMG activity as assessed by Dynamic Gait Analysis	Assessment of head, trunk and joint positions during walking using a 12 camera Vicon motion analysis system. Surface EMG analysis using a 16 channel wireless surface electromyographic (sEMG) system. Assessment of lower limb joint moments and powers using Kistler 9281 and AMTI OPT 400600 force plates.	Within 6 months of recruitment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gait pattern over one year	Comparison of two gait analysis studies taken 12 months apart	12 months after first analysis
Effect on gait pattern of using wrist splints	Assessment of repeat gait analysis measurements done at first visit whilst wearing wrist splints	Within 6 months of recruitment
Effect on gait pattern of lower limb surgery	Further gait analysis studies will be done if a child undergoes any lower limb orthopaedic surgery during the study period and compared with pre-surgery analyses	Within 3 and 6 months of any lower limb surgery

Collaborators and Investigators

• Sponsor: Birmingham Women's and Children's NHS Foundation Trust
• Collaborators: BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): June 3, 2014

Study Record Updates

• Last Update Posted (Estimate): July 28, 2016
• Last Update Submitted That Met QC Criteria: July 27, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Mucopolysaccharidosis; GALNS; Morquio; Galactosamine-6-Sulfatase
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; Mucopolysaccharidoses; Osteochondrodysplasias; Mucopolysaccharidosis IV
• Other Study ID Numbers: 14/WM/0120