DALYs for rare disease surveillance: real-world SMA burden in Belgium during 2018–2024

Background

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder with five clinical types (0-IV) differing in onset and severity. Historically associated with high childhood mortality and lifelong disability, the burden of SMA is evolving following the introduction of disease‑modifying treatments (DMTs) in 2017 and newborn screening in 2022 in Belgium. Standardized population‑level metrics are needed to expand monitoring of disease burden. The aim of this study is to quantify the burden of disease of SMA in Belgium from 2018 to 2024, using real-world data from the Belgian Neuromuscular Disease Registry (BNMDR‑SMA).

Methods

The burden of SMA was quantified using disability‑adjusted life years (DALYs), which sum the Years of life lost due to premature mortality (YLL) and Years lived with disability (YLD). YLLs were calculated from deaths recorded in the BNMDR-SMA. YLDs were calculated from symptoms in the BNMDR-SMA using a prevalence based approach with a novel symptom‑based disease model with six health states mapped to Global Burden of Disease disability weights, and multiplicative multimorbidity correction.

Results

Preliminary SMA DALYs per year in Belgium ranged between 928 in 2018 to 409 in 2021. While overall population burden was low due to low prevalence (1.8-2.4/100 000), per‑case burden was substantial. In 2023, per-case DALYs were 2.8, consisting of 2.2 YLLs (81%) and 0.6 YLDs (19%). Heterogeneity was observed across SMA types: per-case YLDs were 1.8 times higher in type I than in type IV. Per-case YLDs remained stable over time in the overall SMA population, whereas among individuals aged ≤18 years, they decreased by 10%, indicating a decline in non-fatal burden.

Conclusions

This registry‑based DALY framework enables standardized quantification of real-world SMA‑attributable burden. Integrating DALYs into rare disease surveillance could inform evaluation of population‑level effects of DMTs and newborn screening for health policy decision‑making.

Key messages

• DALYs can provide key real-world follow-up for rare disease policy and treatment impact on a population level, supporting evidence based decision making through monitoring.

• Adapting the DALY framework to SMA allows comparable estimates of clinical disease burden, showing rare diseases can in the future be included in burden of disease studies and monitoring.