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

Recent epidemiological studies on the general population reveal that up to 1.3% have oligo/asymptomatic hyperCKemia.

This guideline aims to provide updated, evidence-based recommendations on investigating persons older than 18 years.

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.

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).

An evidence-based guideline is suggested for when and how to investigate adults with oligo/asymptomatic hyperCKemia.