07PA multicenter retrospective cross-sectional study of juvenile-onset anti-HMGCR myopathy

Anti-HMGCR antibody-positive immune-mediated necrotizing myopathy (IMNM) is a distinct subtype of inflammatory myopathy. Although increasingly recognized in children, its clinical features remain under-characterized. Juvenile-onset anti-HMGCR myopathy was defined as seropositive for anti-HMGCR antibodies with onset of hyperCKemia (with or without proximal muscle weakness) before the age of 18, and exclusion of toxin-, drug-, or infection-related myopathies. We retrospectively analyzed patients with juvenile-onset anti-HMGCR myopathy from four hospitals in China between 2010 and 2024. Clinical features, muscle pathology, and response to immunotherapy were assessed. Thirty patients were included (66.7% female), with a median onset age of 8.5 years. Ten (33.3%) presented with asymptomatic hyperCKemia. Among those with weakness, 8 had acute/subacute and 12 chronic onset. No patient had statin exposure; 4 had preceding infections. Median diagnostic delay was 2 years; 8 had delays >10 years. At onset, all had proximal lower limb weakness, 65% axial weakness, increasing to 95.8% during follow-up. Three required long-term ventilation; one died of respiratory failure. Muscle biopsies (n=28) showed fiber size variation (89.3%) and necrosis/regeneration (78.6%). Even patients with isolated hyperCKemia showed pathological changes. Among 24 treated patients, response rates were 50% (steroids + 1 IS), 33% (steroids + 2 IS), and 71.4% (steroids + IVIG + IS). Juvenile-onset anti-HMGCR myopathy may initially present as asymptomatic hyperCKemia yet show significant pathological and functional deterioration over time. Respiratory failure is a significant cause of morbidity and mortality as the disease progresses. Early recognition and IVIG-based therapy are critical to improve outcomes.