Pediatric HyperCKemia: a 13-year retrospective study and predictors of neuromuscular disease and metabolic myopathy

HyperCKemia is a frequent laboratory finding in pediatric practice and may reflect a wide spectrum of conditions, ranging from benign transient states to rare primary neuromuscular disorders. The lack of pediatric-specific diagnostic algorithms complicates risk stratification and clinical decision-making. A retrospective cohort study was conducted, including patients under 18 years of age with hyperCKemia referred to a tertiary reference center between January 2017 and December 2024. Clinical, laboratory, genetic, and histological data were collected. Statistical analyses included univariate testing and logistic regression to identify predictors of primary disease. A total of 119 patients were included (median age 10 years; 76.5% male). Most were symptomatic at presentation (87.4%), and 80.3% met criteria for rhabdomyolysis. A primary disorder was identified in 25.2% of patients, while 52.1% had secondary causes, predominantly viral myositis, and 22.7% remained undiagnosed. Metabolic myopathies accounted for the majority of primary diagnoses (60.0%), followed by muscular dystrophies (23.3%) and inflammatory myopathies (13.3%). Persistent hyperCKemia and male sex emerged as strong independent predictors of primary disease (OR 8.5 and 5.1, respectively). Muscle weakness and exercise intolerance were exclusive to primary disorders. Genetic testing yielded a diagnosis in 26.8% of tested patients, with targeted next-generation sequencing proving particularly valuable. CONCLUSIONS: In pediatric hyperCKemia, persistent CK elevation and male sex are key predictors of underlying primary neuromuscular disease. A phenotype-driven, stepwise diagnostic approach incorporating early genetic testing may improve diagnostic yield and optimize resource utilization. WHAT IS KNOWN: • HyperCKemia in children is most frequently secondary to benign conditions such as viral myositis, while primary neuromuscular disorders are less common but clinically significant. • Creatine kinase levels lack specificity, and the diagnostic approach increasingly relies on genetic testing. WHAT IS NEW: • Persistent hyperCKemia and male sex were identified as independent predictors of primary disease. • Most primary disorders occurred in patients with CK over 1000 UI/L, and higher inter-crisis CK levels were associated with an increased likelihood of underlying disease.