EAN 2024 Guideline on the Diagnostic Approach to Oligo/Asymptomatic HyperCKemia

Background: Recent epidemiological studies on the general population reveal that up to 1.3% have oligo/asymptomatic hyperCKemia. Objective: This guideline aims to provide updated, evidence-based recommendations on investigating persons older than 18 years. Methods: The guideline followed EAN standard operating procedures and was developed according to the GRADE methodology. Fourteen neuromuscular experts from the EAN neuromuscular group were joined by a methodologist and a patient representative. There are two types of recommendations: evidence-based recommendations, based on published studies, and consensus statements if the quality of evidence is poor. Results: We recommend that: (1) Persistent oligo/asymptomatic hyperCKemia with a CK > 1.5 ULN be investigated (Consensus statement); (2) Neurogenic and non-neuromuscular causes of hyperCKemia be excluded (Expert opinion); (3) A Dried Blood Spot (DBS) be done (Strong recommendation); (4) A NCS/EMG to identify whether there is a myopathy or neuropathy be performed (Weak recommendation); (5) A resting lactate and fasting acyl-carnitine assays, if a metabolic myopathy is suspected, be done (Consensus statement); (6) A skeletal muscle MRI be performed to guide/interpret genetic testing (Strong recommendation); (7) NGS is recommended over sequential gene testing (Consensus statement); (8) NGS is recommended over muscle biopsy (Strong recommendation); (9) A muscle biopsy may be offered, if genetic testing is uninformative and one or more applies: a genetic variant of unknown significance (VUS), suspected metabolic myopathy, suspected inflammatory myopathy, abnormal muscle MRI, a CK ≥ 3 ULN, a family history of muscle disease or age, less than 25 years (Expert opinion). Conclusions: An evidence-based guideline is suggested for when and how to investigate adults with oligo/asymptomatic hyperCKemia.