Clinical Trial: MRI and Muscle Involvement in Patients With Mutations in GMPPB

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

Brief Summary:

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.


Detailed Summary:
Sponsor: Rigshospitalet, Denmark

Current Primary Outcome: 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).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: December 1, 2015
Date Started: November 2015
Date Completion:
Last Updated: April 5, 2016
Last Verified: April 2016