MRI and Muscle Involvement in Patients With Mutations in GMPPB

Study Overview
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Brief Summary
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Limb girdle muscular dystrophies (LGMD) are a very heterogeneous group of muscle disorders characterized by muscle weakness and atrophy of the proximal muscles of the shoulder and pelvic girdles. LGMD is classified based on its inheritance pattern and genetic cause into more than 31 different types. A new type - type 2T has been found. The genetic cause of type 2T is mutations in Guanosine Diphosphate (GDP)-mannose pyrophosphorylase B (GMPPB). Mutations in GMPPB can also cause Congenital muscular dystrophies (CMD). Only 41 patients with mutations in GMPPB has been reported. In this study, the investigators examine five new cases with the LGMD phenotype. The primary aim is to examine the muscle involvement using MRI.

Official Title
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MRI and Muscle Involvement in Patients With Mutations in GMPPB

Conditions
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Limb-girdle Muscular Dystrophy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persons with genetically verified mutations in GMPPB Exclusion Criteria: All contraindications for undergoing an MRI scan

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with LGMD 2T<br>Four patients over 18 years old with genetically verified LGMD 2T. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI scan for qualitative analysis of muscle involvement | The MRI protocol include T1-weighted brain and whole body examination. Four cross-sectional slices at shoulder, lumbar back, thigh and calf are chosen for qualitative analysis using the grading scale developed by Mercuri et al. (2007). | One MRI scan per subject (exam lasts approximately 60 min.) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle biopsy for biochemical investigation | Muscle biopsies from the tibialis anterior muscle and the deltoid muscle will be analyzed for glycosylated α-dystroglycan, merosin and GMPPB. (Concentration determined by standard biochemical analysis). | One muscle biopsy per subject (last approximately 15 min.) | 
| 10 meter walk test | Measurement of the time it takes to walk 10 meters. | Exam last approximately 5 min. | 
| Neurological examination and test of muscle strength | Muscle strength (in arms and legs) will be examined based on the Medical Research Council (MRC) scale. | Exam last approximately 15 min. | 
| Questionnaires | Data will be collected using Minimal mental examination (MMSE) and Fatigue Severity Scale (FSS). | Data will be collected once for patients with LGMD 2T (exam last approximately 45 min.) | 
| Heart examination | Echocardiography and Electrocardiogram (ECG). | Exam last approximately 45 min | 
| Forced Vital Capacity (FVC) | FVC is measured as the best of three attempts using a hand-held spirometer. | Exam last approximately 15 min | 
| Electromyography (EMG) | EMG is used for measuring nerve conducting velocity and neuromuscular activity. | Exam last approximately 30 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, LGMD, GMPPB