A.P.13: Myotonic discharges in autophagic vacuolar myopathies: A potential electrophysiologic marker

Abstract

Disordered lysosomal function within muscle cells is the basis for a group of diseases referred to as autophagic vacuolar myopathies. These disorders include acid maltase deficiency (Pompe disease), LAMP-2 deficiency (Danon disease), and X-linked myopathy with excess autophagy (XMEA). We present a 65year old diabetic woman with bilateral leg weakness evolving over 2years to the point she was unable to ambulate without assistance. There was no family history of a similar disorder. She had prominent weakness in her legs proximally>distally while arms and bulbar muscles had normal strength. Mild percussion myotonia of forearm muscles was present but not hand grasp myotonia. CK was 914. Acid alpha-glucosidase activity was normal. Nerve conduction studies showed evidence of a largely axonal neuropathy likely related to her poorly controlled diabetes. Needle exam demonstrated fibrillations and frequent short duration myotonic discharges in arm and leg muscles. Quadriceps muscle biopsy showed basophilic cytoplasmic stippling within myofibers that corresponded to small vacuoles discernable by enzyme histochemical staining for acetylcholinesterase and immunostaining for dystrophin and other sarcolemmal proteins. Cytoplasmic clusters of lysosomes and autophagosome extrusion with duplication of basement membranes were observed with electron microscopy. The biopsy findings are those of an autophagic vacuolar myopathy, the underlying nature of which has not been defined. Frequent short duration myotonic discharges were a remarkable feature. The presence of myotonic discharges has been previously reported to occur in patients with Pompe disease, Danon disease, and XMEA. These discharges indicate hyperexcitability of the muscle membranes and may reflect structural sarcoplasmic changes. Their occurrence in the various disorders involving autophagy suggests that short myotonic discharges may be a diagnostically useful electrophysiologic marker for this group of disorde.