A study using Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in Patients with Limb Girdle Muscular Dystrophy 2I (LGMD2I); an assessment of muscle damage

Background

Re-defined in 1995, the LGMDs are progressive muscular dystrophies. They are defined by high levels of creatine kinase (CK) and dystrophic features on muscle biopsy.

Currently, LGMDs are divided into autosomal dominant (LGMD1) and autosomal recessive (LGMD2) disorders.

A letter is added to the name to show the genetic mutation. LGMD2I is caused by a mutation in the FKRP gene and manifests temporal variability.

Clinically the age of onset, rate of progression and severity varies between cases and even within the same family.

They range from asymptomatic patients with a little hike in CK levels to those severely affected and non-ambulant.

Breathing and heart complications occur in 30% and 60% of patients respectively. The complications occur independently of each other and of the general muscle weakness.

MRI has been used more and more in patients with neuromuscular disorders over the past 5 years.

MRI could identify the muscles involved in the different disorders. It could thus help their diagnosis.

In both LGMD2A and LGMD2I the back thigh muscles are mainly involved. But in LGMD2A there is also selective involvement of other muscles in the lower leg, not seen in LGMD2I.

It is has been shown that MRI findings match those of clinical examination. But sometimes MRI can detect abnormalities on muscle groups that seem normal in clinical tests.

Therefore, MRI can help to show early appearance of a disease and to monitor the effect of early treatments.

Beside MRI another non-invasive technique to consider is phosphorus magnetic resonance spectroscopy (P-MRS).

P-MRS has detected many metabolic abnormalities in the skeletal muscle of patients with LGMD2C-F and some other Muscular Dystrophies.

Primary objective

To develop and test non-invasive methods for assessment of muscle disease and its progression over time in LGMD2I. This could be a useful tool for monitoring response to treatment and therapies.

This will be achieved by measuring static MRI over 2 years and comparing this to age matched adult controls including measuring fat. At the same time we will also be checking if metabolic abnormality is detected in these patients.