Monoclonal Gammopathy – the common denominator of sporadic late-onset nemaline myopathy and paraproteinemic neuropathy

Sporadic late-onset nemaline myopathy (SLONM) is an acquired adult-onset myopathy characterized by subacute proximal weakness and nemaline rods in muscle. Although SLONM frequently occurs with monoclonal gammopathy of undetermined significance (MGUS), the coexistence with other MGUS-related disorders has not been reported. We describe three patients with SLONM and paraproteinemic neuropathy, showing sensory involvement and variable motor deficits, from mild non-progressive disease to a severe form with bulbar complications. Muscle histology revealed a significant number of fibres with nemaline rods and also frequent mitochondrial abnormalities, while nerve pathology demonstrated granular endoneurial deposits consistent with immune-complex-mediated neuropathy. One untreated patient remained stable, whereas the other two progressive, immunosuppressive-refractory cases improved with anti-plasma cell therapy. These cases illustrate a previously unreported co-occurrence of SLONM and MGUS-associated neuropathy. Despite differing clinical courses, shared pathology suggests common mechanisms, with mitochondrial abnormalities as a possibly under-recognized feature. Muscle and nerve biopsy including electronmicroscopic analysis is crucial for accurate diagnosis, and clone-directed therapy may provide benefit.