Patterns of clinical progression among patients with autosomal recessive limb-girdle muscular dystrophy (LGMDR): A systematic review


Clinical Management

Poster Number: 90


Antoinette Cheung , Ivana F Audhya , Shelagh M Szabo MSc, Michael Friesen , Conrad C Weihl , Katherine L Gooch PhD


1. Broadstreet Health Economics and Outcomes Research, 2. Sarepta Therapeutics, Inc., 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 frequency of loss of ambulation (LOA) among patients with LGMDR, and progression to cardiac and respiratory abnormalities among those with and without LOA.
Background: Patients with LGMDR may experience muscle weakness progressing to severe impairments affecting their mobility, cardiac function, and respiratory function. The clinical course of LGMDR is highly variable; some patients have rapid onset and early progression with significant morbidity such as LOA.
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 number and percentage n(%) of patients with vs. without LOA who experienced cardiac or respiratory abnormalities, and mean (standard deviation, SD) age at LOA, cardiac, and respiratory abnormalities.
Results: From 2,929 abstracts screened, 418 patients were identified with data on ambulatory status. LOA was reported in 265 (63.4%), and case counts by subtype ranged from 5 (LGMDR12) to 105 (LGMDR3-6). Thirty-four percent (n=142) of patients with LOA had reports of cardiac and/or respiratory function status. Among these patients, respiratory abnormalities were most frequent in LGMDR3-6 (74.1%); and cardiac, in LGMDR9 (73.3%). The mean (SD) age at cardiac abnormalities was earliest in LGMDR9 (23.7 [17.7] years; in 73.3%); and respiratory abnormalities, earliest in LGMDR3-6 (23.9 [11.0] years; in 74.1%). Abnormalities were less common in patients without LOA except in LGMDR9, where abnormalities remained frequent (71.4% respiratory, 52.4% cardiac).
Conclusions: This study described the co-occurrence of LOA, cardiac, and respiratory abnormalities in LGMDR. Caution should be taken when interpreting summary estimates as these are impacted by the frequency of underlying genotypes; an additional limitation is that data derived from case reports lack standardized reporting. Despite limited data, these findings help characterize the clinical progression of LGMDR.