An autosomal recessive variant in PYGM causes myophosphorylase deficiency in Red Angus composite cattle.

BACKGROUND: Between 2020 and 2022, eight calves in a Nebraska herd (composite Simmental, Red Angus, Gelbvieh) displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover. Available sire pedigrees contained a paternal ancestor within 2-4 generations in all affected calves. Pedigrees of the calves' dams were unavailable, however, the cows were ranch-raised and retained from prior breeding seasons, where bulls used for breeding occasionally had a common ancestor. Therefore, it was hypothesized that a de novo autosomal recessive variant was causative of exercise intolerance in these calves. RESULTS: A genome-wide association analysis utilizing SNP data from 6 affected calves and 715 herd mates, followed by whole-genome sequencing of 2 affected calves led to the identification of a variant in the gene PYGM (BTA29:g.42989581G > A). The variant, confirmed to be present in the skeletal muscle transcriptome, was predicted to produce a premature stop codon (p.Arg650*). The protein product of PYGM, myophosphorylase, breaks down glycogen in skeletal muscle. Glycogen concentrations were fluorometrically assayed as glucose residues demonstrating significantly elevated glycogen concentrations in affected calves compared to cattle carrying the variant and to wild-type controls. The absence of the PYGM protein product in skeletal muscle was confirmed by immunohistochemistry and label-free quantitative proteomics analysis; muscle degeneration was confirmed in biopsy and necropsy samples. Elevated skeletal muscle glycogen persisted after harvest, resulting in a high pH and dark-cutting beef, which is negatively perceived by consumers and results in an economic loss to the industry. Carriers of the variant did not exhibit differences in meat quality or any measures of animal well-being. CONCLUSIONS: Myophosphorylase deficiency poses welfare concerns for affected animals and negatively impacts the final product. The association of the recessive genotype with dark-cutting beef further demonstrates the importance of genetics to not only animal health but to the quality of their product. Although cattle heterozygous for the variant may not immediately affect the beef industry, identifying carriers will enable selection and breeding strategies to prevent the production of affected calves.

Pseudohyperkalemia in horses with rhabdomyolysis reported by an enzymatic chemistry analyzer.

OBJECTIVE: To investigate pseudohyperkalemia occurring in horses experiencing rhabdomyolysis when serum chemistry profiles are run on an VetScan VS2 analyzer (Abaxis). ANIMALS: 18 horses with rhabdomyolysis (creatine kinase [CK] > 1,000 U/L). METHODS: In 3 horses with serum CK activities > 5,800 U/L and persistent serum potassium concentrations of > 8.5 mmol/L (VetScan VS2), potassium concentrations were reevaluated with either i-STAT Alinity Base Station (Abbott), Catalyst (Idexx), or Cobas c501 (Roche) ion-specific analyzers. Paired serum samples from 15 additional horses (median serum CK activity, 7,601 U/L; range, 1,134 to 192,447 U/L) were analyzed on both VetScan VS2 and Cobas c501 machines. Serum potassium concentrations were compared between the VetScan VS2 and ion-specific analyzers by Bland-Altman and Wilcoxon ranked tests and correlated to log10 CK activity via Pearson correlation. RESULTS: Serum potassium concentrations were significantly higher on the VetScan VS2 (6.7 ± 1.6 mmol/L) versus the ion-specific analyzers (4.0 ± 1.1 mmol/L; P < .0001), with high bias shown in Bland-Altman analysis (43.1 ± 27.9). Potassium concentrations positively correlated with log10 CK activity with the VetScan VS2 (R2 = 0.51; P = .003) but not the Cobas (R2 = 0.09; P = .3) analyzer. CLINICAL RELEVANCE: An alternate analyzer to the VetScan VS2 should be used to evaluate serum potassium concentrations in horses with rhabdomyolysis because the VetScan VS2 methodology uses lactate dehydrogenase, which increases in serum with rhabdomyolysis and falsely elevates potassium concentrations.