MRI and Muscle Involvement in Patients With Mutations in GMPPB
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.
|Limb-girdle Muscular Dystrophy|
|Study Design:||Observational Model: Case-Only
Time Perspective: Cross-Sectional
|Official Title:||MRI and Muscle Involvement in Patients With Mutations in GMPPB|
- MRI scan for qualitative analysis of muscle involvement [ Time Frame: One MRI scan per subject (exam lasts approximately 60 min.) ]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).
- Muscle biopsy for biochemical investigation [ Time Frame: One muscle biopsy per subject (last approximately 15 min.) ]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).
- 10 meter walk test [ Time Frame: Exam last approximately 5 min. ]Measurement of the time it takes to walk 10 meters.
- Neurological examination and test of muscle strength [ Time Frame: Exam last approximately 15 min. ]Muscle strength (in arms and legs) will be examined based on the Medical Research Council (MRC) scale.
- Questionnaires [ Time Frame: Data will be collected once for patients with LGMD 2T (exam last approximately 45 min.) ]Data will be collected using Minimal mental examination (MMSE) and Fatigue Severity Scale (FSS).
- Heart examination [ Time Frame: Exam last approximately 45 min ]Echocardiography and Electrocardiogram (ECG).
- Forced Vital Capacity (FVC) [ Time Frame: Exam last approximately 15 min ]FVC is measured as the best of three attempts using a hand-held spirometer.
- Electromyography (EMG) [ Time Frame: Exam last approximately 30 min ]EMG is used for measuring nerve conducting velocity and neuromuscular activity.
|Study Start Date:||November 2015|
|Study Completion Date:||April 2016|
|Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Patients with LGMD 2T
Four patients over 18 years old with genetically verified LGMD 2T.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02635321
|Copenhagen Neuromuscular Center|
|Copenhagen, Denmark, 2100|
|Principal Investigator:||Sofie T Østergaard, Bsc.||Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University|