43PSporadic late-onset nemaline myopathy with monoclonal gammopathy: defining a more aggressive subtype with worse prognosis

Abstract

Sporadic Late-Onset Nemaline Myopathy (SLONM) is an adult-onset acquired myopathy characterized by progressive weakness and, in severe cases, respiratory involvement. A notable proportion is associated with monoclonal gammopathy of undetermined significance (SLONM-MGUS), suggesting an immune-mediated pathogenesis. Although the presence of monoclonal gammopathy has known clinical and therapeutic implications, its contribution to disease severity and progression remains poorly defined. To assess clinical, histological, and prognostic differences between SLONM patients with (SLONM-MGUS) and without (SLONM-noMGUS) monoclonal gammopathy through a systematic review and single-center analysis. We reviewed literature spanning 25 years and included five patients from our institution (Sant’Andrea Hospital, SAPIENZA University of Rome). Clinical presentations, histopathological features, treatments, and outcomes were compared between SLONM-MGUS and SLONM-noMGUS groups. Of 144 cases analyzed, 47% had SLONM-MGUS. This subgroup exhibited a more severe course, with higher rates of respiratory and cardiac involvement (p<0.05), and reduced treatment responsiveness. Serum creatine kinase (CK) levels were mildly elevated overall (mean 203.7 U/L), but predominantly normal in SLONM-MGUS (p = 0.01). Muscle biopsies in SLONM-MGUS patients showed more abundant nemaline rods, frequently accompanied by cytoplasmic bodies, and lobulated fibers, though often requiring repeat biopsies. Necrosis and inflammatory infiltrates were less frequent in this subgroup. Common treatments included corticosteroids, IVIg, and autologous stem cell transplantation (ASCT), However, complete recovery was rare, especially among SLONM-MGUS patients (p < 0.001), who also exhibited higher mortality and poorer prognosis. SLONM-MGUS represents a clinically distinct and more aggressive variant, frequently leading to worse outcomes. These findings highlight the need for early recognition and tailored therapeutic strategies.