The objective was here to describe a large series of patients with α, β and γ sarcoglycanopathies (LGMD-R3, R4 and R5 in the new nomenclature) and to study the phenotypic correlations and the progression of the disease.
In this context, a retrospective multicenter study in 4 centers in the region of Paris collecting neuromuscular, respiratory, cardiac, histological and genetic data. The primary outcome measure for progression was age of loss of mobility (LoA); the severity of the disease was established according to the LoA before or after 18 years.
One hundred patients (54 γ-SG; 41 α-SG; 5 β-SG) from 80 families were included. Clinicians have observed that:
- The γ-SG patients had an earlier disease onset than the α-SG patients (5.5 vs 8 years, p = 0.022) and the β-SG patients (24.4 years).
- Axial muscle weakness and joint contractures were common and exertion intolerance was observed. At a mean follow-up of 22.9 years, 65.3% of patients were in a wheelchair (66.7% α-SG, 67.3% γ-SG, 40% β-SG).
- Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, particularly in γ-SG patients (p = 0.01).
- Thirty patients were ventilated and 6 died.
- Lack of sarcoglycan protein expression on muscle biopsy and an earlier age of onset were associated with earlier time to LoA (p = 0.021 and p = 0.002).
- Age of onset was an independent indicator of both severity and time to LoA (p = 0.0004 and p = 0.009).
- The α-SG patients showed genetic heterogeneity, while> 90% of the γ-SG patients carried the homozygous c.525delT variant.
Five new mutations have been identified.
The authors conclude that this large multicenter series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at onset is an independent indicator of disease severity and LoA and should be considered in future clinical trials.
