Clinicopathological and imaging differences between pediatric and adult patients with anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase necrotizing myopathy

We aimed to elucidate the clinicopathological and imaging differences between pediatric and adult patients with anti-hydroxy-3-methyl-glutaryl-coenzyme A reductase (anti-HMGCR) myopathy. A series of 111 patients with anti-HMGCR myopathy were divided into pediatric (33 patients, onset age < 18 years) and adult (78 patients, onset age ≥ 18 years) groups. Clinical, imaging, and pathological characteristics were compared between the groups. Overall median age at onset was 40 years. Median duration of disease was 12 months. The male:female ratio was 41:70. Prevalence of statin exposure was 0% in the pediatric group and 21% in the adult group (P < 0.001). The prevalence of severe weakness was significantly higher in the pediatric group (63.6% vs. 36.4%; P = 0.008). Myalgia was significantly more frequent in adults (49.3% vs. 20.8%; P = 0.03). The median serum creatine kinase (CK) concentration was significantly higher in the pediatric group (7263.0 vs. 3388.5U/L; P = 0.03). Magnetic resonance imaging of the thigh revealed muscle edema in 82.8% of patients and fatty infiltration in 60.9%. Muscle edema scores in the sartorius (P = 0.02) and gracilis (P = 0.03) were significantly higher in the pediatric group. Fatty infiltration score was significantly correlated with disease duration (r = 0.51; P < 0.001). Dystrophic pathology was significantly more frequent in pediatric patients (47% vs. 8%; P = 0.001). Regeneration score was significantly higher in pediatric group (P = 0.025). Sarcolemmal deposition of membrane attack complex (MAC) was significantly greater in pediatric patients (P = 0.010) and correlated significantly with manual muscle testing-8 score (r = - 0.14; P = 0.04) and serum CK concentration (r = 0.36; P = 0.002). Pediatric patients presented with more severe weakness, higher CK concentration, higher muscle edema score in the sartorius and gracilis, more muscle regeneration, more sarcolemmal MAC deposition, and dystrophic pathology. Adult patients exhibited more myalgia and more minimal changes. Sarcolemmal MAC deposition is a biomarker for disease activity.