A contemporary analysis of the Australian clinical and genetic landscape of spinal muscular atrophy: a registry based study

Lakshmi Balaji; Robin Forbes; Anita Cairns; Hugo Sampaio; Andrew J Kornberg; Lauren Sanders; Phillipa Lamont; Christina Liang; Kristi J Jones; Kristen Nowak; Cullen O'Gorman; Ian Woodcock; Nancy Briggs; Eppie M Yiu; Michelle A Farrar; Didu Kariyawasam

doi:10.1016/j.lanwpc.2024.101237

A contemporary analysis of the Australian clinical and genetic landscape of spinal muscular atrophy: a registry based study

Lancet Reg Health West Pac. 2024 Nov 6:53:101237. doi: 10.1016/j.lanwpc.2024.101237. eCollection 2024 Dec.

Authors

Lakshmi Balaji^{1

2}, Robin Forbes³, Anita Cairns⁴, Hugo Sampaio¹, Andrew J Kornberg⁵, Lauren Sanders^{6

7}, Phillipa Lamont⁸, Christina Liang⁹, Kristi J Jones^{10

11}, Kristen Nowak¹², Cullen O'Gorman^{13

14}, Ian Woodcock⁵, Nancy Briggs¹⁵, Eppie M Yiu^{3

5

16}, Michelle A Farrar^{1

2}, Didu Kariyawasam^{1

2}

Affiliations

¹ Department of Neurology, Sydney Children's Hospital Randwick, NSW, Australia.
² Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
³ Australian Neuromuscular Disease Registry, Neuroscience Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁴ Queensland Children's Hospital, Brisbane, QLD, Australia.
⁵ Department of Neurology, The Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁶ The University of Melbourne, VIC, Australia.
⁷ St Vincent's Hospital, Melbourne, VIC, Australia.
⁸ Royal Perth Hospital, Perth, WA, Australia.
⁹ Royal North Shore Hospital, St Leonards, NSW, Australia.
¹⁰ Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia.
¹¹ Children's Hospital at Westmead, Westmead, NSW, Australia.
¹² University of Western Australia, Perth, WA, Australia.
¹³ Princess Alexandra Hospital, Brisbane, QLD, Australia.
¹⁴ University of Queensland, Brisbane, QLD, Australia.
¹⁵ Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia.
¹⁶ Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.

Abstract

Background: New paradigms of diagnosis and treatment have changed the neurodegenerative trajectory for individuals with spinal muscular atrophy (SMA). Registries are a critical tool to provide real-world data on treatment patterns, their effects and health care provision within this evolving paradigm of care. This study aimed to evaluate the phenotypic and genotypic landscape, treatment patterns and health impact of SMA in Australia through the national registry.

Methods: This cross-sectional study investigated demographic, clinical and genetic information, sequelae of weakness, treatment patterns and patient-reported outcomes amongst individuals with SMA enrolled in the Australian Neuromuscular Disease Registry (ANMDR) from 1st January 2020 to 30th April 2023. Descriptive statistics were used for analysis and Chi-Squared or Fisher's exact tests for associations.

Findings: 195 individuals with SMA enrolled into the ANMDR. 5/195 (2.6%) were deceased by censor date. Of (n = 190) individuals living with SMA, 104/190 (54.7%) were children. Minimum Australian prevalence was 0.73/100,000. SMN2 copies were inversely associated with phenotype in those with homozygous SMN1 deletions (p < 0.0001)). Treatment was utilised in 154/190 (81%) of the population, with 65/137 (47.6%) of individuals perceiving improvements with therapeutic intervention on Patient/Parent Global Impression of Improvement scale (p < 0.0001). Engagement with multidisciplinary care practitioners was significantly higher among children with SMA than adults (93% versus 12%, p < 0.0001).

Interpretation: Despite diagnostic and therapeutic advances, mortality and the multi-systemic health impact of SMA continue to be experienced within the Australian population. Healthcare provision must align with patient-centred outcomes, adapting to meeting their changing but ongoing care requirements. The study identified the considerable unmet need for multidisciplinary care, not only for adults with SMA but also for the emerging cohort of treated children, emphasising the imperative for comprehensive healthcare provision to address their evolving needs.

Funding: No funding was received for this study.

Keywords: Comorbidities; Epidemiology; Prevalence; Rare disease; Registry; Spinal muscular atrophy.