Progression to loss of ambulation (LOA) among patients with autosomal recessive limb-girdle muscular dystrophy (LGMDR): A systematic review


Clinical Management

Poster Number: 92


Ivana Audhya MSc, Antoinette Cheung , Shelagh M Szabo MSc, Emma Flint , Conrad C Weihl , Katherine L Gooch PhD


1. Sarepta Therapeutics, Inc., 2. Broadstreet Health Economics and Outcomes Research, 3. Broadstreet Health Economics and Outcomes Research, 4. Broadstreet Health Economics and Outcomes Research, 5. Washington University School of Medicine, 6. Sarepta Therapeutics, Inc.

Objective: To characterize the time from disease onset to LOA among patients with LGMDR.

Background: Patients with LGMDR predominantly present with proximal muscle weakness; severity varies widely between patients. Progression to severe mobility impairments such as LOA has been described; however, it is unclear how the occurrence and timing of LOA compares between subtypes and by age at onset.

Methods: A systematic review was conducted using MEDLINE and EMBASE focusing on the most common LGMDR subtypes: LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, LGMDR12. Data were derived from cohort studies and case reports. Outcomes of interest were frequency of and mean (standard deviation [SD]) time from onset to LOA among those with adult-, late childhood- (10-18 years), and early childhood-onset LGMDR (<10 years).

Results: From 2,929 abstracts, 375 patients were identified with age at LGMD onset and ambulatory status reported, with case counts ranging from 20 (LGMDR12) to 113 (LGMDR2/MM). Among patients with LOA (n=228), adult-onset disease was least common in LGMDR3-6 (1.5%) and most common in LGMDR2 (46.5%); LGMDR3-6 cases with LOA primarily had early childhood-onset (84.8%). Mean (SD) time to LOA varied between subtypes, being shortest for patients with early childhood-onset LGMDR9 (12.0 [4.9] years, n=19) and longest for those with late childhood-onset LGMDR2 (21.5 [12.5] years, n=21).

Conclusions: These findings suggest that patients with early childhood-onset disease tend to have faster progression to LOA than those with late childhood- or adult-onset disease, particularly in LGMDR9. Caution should be taken when interpreting summary estimates as these are impacted by the frequency of the underlying genotypes; an additional limitation is that data derived from case reports lack standardized reporting. Nevertheless, these findings provide a greater understanding of progression to LOA by subtype in LGMDR.