Troponin T is elevated in a relevant proportion of patients with 5q-associated spinal muscular atrophy

Abstract

Troponin T concentration (TNT) is commonly considered a marker of myocardial damage. However, elevated concentrations have been demonstrated in numerous neuromuscular disorders, pointing to the skeletal muscle as a possible extracardiac origin. The aim of this study was to determine disease-related changes of TNT in 5q-associated spinal muscular atrophy (SMA) and to screen for its biomarker potential in SMA. We therefore included 48 pediatric and 45 adult SMA patients in this retrospective cross-sequential observational study. Fluid muscle integrity and cardiac markers were analyzed in the serum of treatment-naïve patients and subsequently under disease-modifying therapies. We found a TNT elevation in 61% of SMA patients but no elevation of the cardiospecific isoform Troponin I (TNI). TNT elevation was more pronounced in children and particularly infants with aggressive phenotypes. In adults, TNT correlated to muscle destruction and decreased under therapy only in the subgroup with elevated TNT at baseline. In conclusion, TNT was elevated in a relevant proportion of patients with SMA with emphasis in infants and more aggressive phenotypes. Normal TNI levels support a likely extracardiac origin. Although its stand-alone biomarker potential seems to be limited, exploring TNT in SMA underlines the investigation of skeletal muscle integrity markers.

Figure 1

TNT treatment-naïve concentrations. A: TNT treatment-naïve concentrations per SMN2 copy numbers, B: TNT treatment-naïve concentration between SMA types, C: TNT treatment-naïve concentrations between adults and children, D: TNT treatment-naïve concentration between male and female adult patients. Adult TNT cut-off (14 ng/L) displayed as dotted line. Whiskers indicate minimum and maximum, circles indicate extreme outliers with an interquartile range > 1.5 – 3 and diamond shapes indicate outliers with an interquartile range > 3. **p < 0.001. Patients identified by newborn screening are not displayed.

Figure 2

Longitudinal dynamic of TNT and skeletal muscle markers (CK, Crn, Myoglobin) in adult patients with SMA under nusinersen. Mean and standard deviation are displayed. TNT cut-off (14 ng/L) displayed as dotted line. Number of patients included in the analyses are indicated in gray. Significant changes from baseline are indicated by *p < 0.05 or **p < 0.001.

Figure 3

Longitudinal display of TNT in adult patients with SMA under nusinersen in sex subgroups. Mean and standard deviation are displayed. TNT cut-off (14 ng/L) displayed as dotted line. Significant changes from baseline are indexed in the respective color as follows: *p < 0.05.