Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis

Background Both type 1 (PSSM1) and type 2 polysaccharide storage myopathy (PSSM2) are characterised by aggregates of abnormal polysaccharide in skeletal muscle. Whereas the genetic basis for PSSM1 is known (R309H GYS1), the cause of PSSM2 in Quarter Horses (PSSM2‐QH) is unknown and glycogen concentrations not defined. Objectives To characterise the histopathological and biochemical features of PSSM2‐QH and determine if an associated monogenic variant exists in genes known to cause glycogenosis. Study design Retrospective case control. Methods Sixty‐four PSSM2‐QH, 30 PSSM1‐QH and 185 control‐QH were identified from a biopsy repository and clinical data, histopathology scores (0–3), glycogen concentrations and selected glycolytic enzyme activities compared. Coding sequences of 12 genes associated with muscle glycogenoses were identified from whole genome sequences and compared between seven PSSM2‐QH and five control‐QH. Results Exertional rhabdomyolysis in PSSM2‐QH occurred predominantly in barrel racing and working cow/roping performance types and improved with regular exercise and a low starch/fat‐supplemented diet. Histopathological scores, including the amount of amylase‐resistant polysaccharide (PSSM2‐QH 1.4 ± 0.6, PSSM1‐QH 2.1 ± 0.3, control‐QH 0 ± 0, p