Progression to Loss of Ambulation Among Patients with Autosomal Recessive Limb-girdle Muscular Dystrophy: A Systematic Review

Abstract

Background The impact of age at autosomal recessive limb girdle muscular dystrophy (LGMDR) onset on progression to loss of ambulation (LOA) has not been well established, particularly by subtype. Objectives: To describe the characteristics of patients with adult-, late childhood-, and early childhood-onset LGMDR by subtype and characterize the frequency and timing of LOA. Methods: A systematic review was conducted in MEDLINE, Embase and the Cochrane library. Frequency and timing of LOA in patients with LGMDR1, LGMDR2/Miyoshi myopathy (MM), LGMDR3-6, LGMDR9, and LGMDR12 were synthesized from published data. Results: In 195 studies, 695 (43.4%) patients had adult-, 532 (33.2%) had late childhood-, and 376 (23.5%) had early childhood-onset of disease across subtypes among those with a reported age at onset (n = 1,603); distribution of age at onset varied between subtypes. Among patients with LOA (n = 228), adult-onset disease was uncommon in LGMDR3-6 (14%) and frequent in LGMDR2/MM (42% ); LGMDR3-6 cases with LOA primarily had early childhood-onset (74% ). Mean (standard deviation [SD]) time to LOA varied between subtypes and was shortest for patients with early childhood-onset LGMDR9 (12.0 [4.9] years, n = 19) and LGMDR3-6 (12.3 [10.7], n = 56) and longest for those with late childhood-onset LGMDR2/MM (21.4 [11.5], n = 36). Conclusions: This review illustrated 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. These findings provide a greater understanding of progression to LOA by LGMDR subtype, which may help inform clinical trial design and provide a basis for natural history studies.

Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review

“…This systematic review describes the clinical progression to LOA, respiratory, and cardiac involvement in LGMDR and the frequency of respiratory or cardiac involvement among those with or without LOA, stratified by subtype. Although previous analyses have evaluated the timing of LOA across different subtypes based on the age of disease onset, 143 data are sparse on the timing of respiratory and cardiac involvement in LGMDR, in particular relative to ambulation loss. 144 A clearer understanding of the clinical progression of LGMDR is important because the occurrence of these more severe outcomes contribute to a greater disease burden.…”

Autosomal Recessive Limb-Girdle Muscular Dystrophy-3: A Case Report of a Patient with Autism Spectrum Disorder

“…Typically, patients with sarcoglycanopathies have a childhood onset of progressive limb-girdle atrophy and loss of ambulation [ 21 ], with varying degrees of cardiac and respiratory involvement. Toe walking in early childhood is often present before muscle weakness is detected.…”