Skeletal Muscle Microbiopsies in Children and Adults—Tolerability, Sample Yield, and Analyzability

ABSTRACT Introduction/Aims Traditional methods of sampling skeletal muscle tissue are invasive. This study aimed to evaluate a sub‐millimeter core‐biopsy (microbiopsy) as a potentially more tolerable method, with further regard to tissue yield and analyzability of RNA expression. Methods Children (9–13 years, n = 11) and adults (18–50 years, n = 16) were recruited. Microbiopsy and venipuncture were performed, with prior application of local anesthesia cream. Additionally, adults underwent a Bergström muscle biopsy, with infiltrative local anesthesia. Pain was rated using the visual analog scale (VAS), reported as medians (95% CI). Microbiopsy samples were freeze‐dried and weighed. To evaluate RNA sequencing performance at low tissue sample weights, a six‐step incremental tissue ladder (10–500 μg) was analyzed. Results Children rated venipunctures and microbiopsies low, at VAS = 0.1 (0.0–0.6) and 1.6 (0.9–3.9), respectively. Microbiopsy pain ratings were slightly higher than venipuncture, p < 0.001. Pain ratings in adults were 0.0 (0.0–0.5), 1.8 (1.3–2.4), 2.9 (2.4–3.8), and 2.7 (2.2–3.8) for venipuncture, microbiopsy, Bergström biopsy, and infiltrative local anesthesia, respectively. Microbiopsy was rated less painful than Bergström biopsy and local anesthesia ( p < 0.05). Children did not rate microbiopsy more painful than adults ( p = 0.82). Microbiopsies yielded on average 303 (SD 121.8) μg. RNA sequencing detected similar transcriptomic signatures across the tissue ladder. Discussion The generally low pain ratings for the microbiopsy procedure support its use as a tolerable method of acquiring skeletal muscle samples in both children and adults. It represents a less painful alternative to Bergström biopsies while still rendering adequate material for RNA sequencing.