Natural History of Morquio B and Late-Onset of GM1 Gangliosidosis

Natural History of Morquio B and Late-Onset GM1 Gangliosidosis

Mucopolysaccharidosis type IVB (Morquio-B disease, MBD) is an autosomal-recessive lysosomal disease caused by mutations in a gene called GLB1. Clinically, Morquio B presents with progressive skeletal deformities involving mostly long bones and spine. While the information on GLB1 mutations associated with MBD is limited, there is a significant overlap in clinical presentation between Morquio B and late-onset GM1 gangliosidosis with both conditions being caused by mutations in the same GLB1 gene. In this study, the investigators plan to collect retrospective data from patients' medical charts, as well as, information from the prospective follow up clinic visits. There will be two study visits with the interval of one year. The study procedures will include a detailed physical exam, bone scans, heart and lung function, physical endurance tests, hearing test, laboratory tests and quality of life surveys.

The purpose of this study is to collect data on the natural history of Morquio B and to create a biobank of laboratory samples (blood, urine and skin cells) for future research. This information will improve the understanding of the natural progression of Morquio B disease.

Study Overview

• Status: Unknown
• Conditions: Morquio B Disease; GM1 Gangliosidosis Type III

Detailed Description

The primary objective of this study is to establish the natural history of Morquio B (Mucopolysaccharidosis type IVB, MBD) disease through the collection and analysis of retrospective and prospective data on patients diagnosed with Morquio B. Because of significant overlap in clinical presentation, patients with late-onset GM1 will also be included.

Upon consent, data from clinical, laboratory, functional and quality of life studies, and data from review of medical records will be collected and analyzed descriptively. In addition, the samples of blood, urine and fibroblasts will be collected and stored at BC Children Hospital Research Institute Biobank for future research. The prospective follow up will include two clinic visits, one year apart. The following data will be collected during the prospective observational part of the study (as per study protocol) and retrospective part (whether such data are available from the medical chart):

• Medical history: Morquio B / Late-onset GM1 gangliosidosis diagnosis, presentation, treatments and symptom progression
• Physical exam, including neurological and ophthalmological assessments
• Standard Grip Strength Evaluation
• Range of motion
• Six-minute walk test (6MWT)
• 3-Minute Stair Climb Test
• Gait and Motion assessment
• Pulmonary function testing
• Hearing test
• Echocardiography
• EKG
• X-ray (lumbar spine, upper & lower limbs, hip)
• DXA scan
• Brain MRI
• Laboratory tests (GAGs assay and pro-inflammatory cytokine panel)
• Blood, urine and fibroblast samples for biobanking
• Genetic test (if not done per standard of care)

Additional assessments and evaluations:

• Patient-reported outcomes: quality of life SF-36, MPS HAQ and the interview on personally meaningful outcomes

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Nataliya Yuskiv, Dr; Phone Number: 6399 6048752000; Email: nyuskiv@cw.bc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H3V4
      • BC Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients of any age, any gender with no previous HSCT procedure, with a confirmed diagnosis of beta-galactosidase deficiency and who clinically present with skeletal dysostosis with or without CNS involvement.

Description

Inclusion Criteria:

• Confirmed diagnosis of beta-galactosidase deficiency via demonstration of deficient enzyme activity and/or demonstration of homozygous/compound heterozygous pathogenic GLB1 variants;
• Patients diagnosed with beta-galactosidase deficiency and who present with "MPSIVB skeletal phenotype" with or without primary CNS involvement;
• Patient / parent or legal guardian is able to read, understand, and sign the informed consent.

Exclusion Criteria:

• Previous Hematopoietic Stem Cell Transplant procedure (HSCT);
• Concurrent disease or condition that would interfere with participation in the study and/or travel to the site (for the prospective follow up);
• Previous or current casual treatments that might affect the natural course of the disease;
• Patient's (guardian's) not understanding and/or not agreeing to the informed consent form;
• GM1-gangliosidosis patients who present without "MPSIVB skeletal phenotype"

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Development	Height	Through study completion, an average of 1 year
Physical Development	Weight	Through study completion, an average of 1 year
Physical Development	Growth rate	Through study completion, an average of 1 year
Physical Endurance	6MWT	1 year
Physical Endurance	3MSCT	1 year
Physical Endurance	Standard Grip Strength evaluation	1 year
Range of Motion Scale	Assessments: shoulder, elbow, wrist, hip, knee, ankle	Through study completion, an average of 1 year
Skeletal involvement	X-ray studies, pQCT (where available), DXA of lateral distal femur, x-ray and/or MRI of cervical spine to assess spinal stenosis and spinal cord compression; X-ray of cervical spine to assess odontoid hypoplasia and atlantoaxial instability	Through study completion, an average of 1 year
CNS involvement	Neurological assessments, Brain MRI	Through study completion, an average of 1 year
Surrogate biomarkers	Glycosaminoglycans (GAGs): keratan sulfate, heparan sulfate, dermatan sulfate, chondroitin-6-sulfate	Baseline and 1 year
Surrogate biomarkers	Comprehensive pro-inflammatory cytokine panel with markers of bone turnover	Baseline and 1 year
Health-related Quality of Life (HRQoL)	SF-36	Baseline and 1 year
Health-related Quality of Life (HRQoL) and Activities of Daily living (ADLs)	MPS-HAQ	Baseline and 1 year
Personally Meaningful Outcomes	PMO Questionnaire	Baseline and 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biobank of samples for the future research	Blood, urine, DBS, fibroblasts (live frozen cells)	1 year

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Medical University of Graz; Hospital de Clinicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): May 31, 2022

Study Registration Dates

• First Submitted: March 17, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Actual): April 30, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Mucopolysaccharidoses; Gangliosidoses; Gangliosidosis, GM1; Mucopolysaccharidosis IV
• Other Study ID Numbers: H18-00155

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No