Progressive Bulbar Weakness and Neuromuscular Paralysis due to Anti-SAE1 Antibody Myositis

Introduction: Subacute neuromuscular paralysis is attributable to a variety of inflammatory, infectious, neurodegenerative, autoimmune, and paraneoplastic etiologies. Bulbar weakness is seen in myasthenia like syndromes as well as brainstem lesions. We present a rare case of neuromuscular failure from idiopathic inflammatory myositis (IIM) due to anti-small ubiquitin-like modifier 1-activating enzyme subunit 1 (SAE1).


Description: A 49-year-old man was admitted to the ICU for evaluation of progressive neuromuscular weakness over 6 months. His symptoms began with dysphagia and dysarthria, followed by proximal weakness progressing to quadriplegia within 6 weeks. He developed dyspnea and respiratory arrest, requiring tracheostomy and mechanical ventilation. On exam, he had minimal distal motor activity, intact extraocular movements, no ptosis, and a bilateral heliotrope rash. Labs revealed acute kidney injury requiring dialysis.
Neuroimaging, CT chest/abdomen, CSF analysis, upper GI endoscopy, and nerve conduction studies were non-revealing. Due to concern for inflammatory myopathy, a comprehensive myositis panel was sent, including anti-Jo1, Mi-2, MDA5, SRP, and anti-SAE1. Empiric therapy with pulse-dose steroids, IVIG, and plasmapheresis was initiated without improvement. Skin biopsy was consistent with dermatomyositis (DM); muscle biopsy showed atrophy without inflammation. Renal biopsy revealed acute tubular necrosis. Serologies were positive for ANA (1:1250) and anti-SAE1 antibodies, others were negative. Despite aggressive therapy, the patient developed pneumonia and died from sepsis and respiratory failure.


Discussion: This case highlights a rare, fulminant presentation of anti-SAE1 IIM, a myositis-specific antibody seen in fewer than 5% of DM cases. Unlike gradual proximal weakness, this patient had bulbar-onset symptoms progressing to paralysis and respiratory failure. Muscle biopsy was non-confirmatory, showing only atrophy, delaying diagnosis. Despite steroids, IVIG, and plasmapheresis, he remained refractory, suggesting a treatment-resistant phenotype.
Early diagnosis of atypical anti-SAE1 IIM, particularly when clinical and biopsy findings diverge, is critical. Recognition of IIM and DM subtypes by broad antibody testing may lead to early initiation of tailored and advanced immunotherapy.