Mitochondrial Myopathy

A deficiency of Complex 1, the first step in the mitochondrial respiratory chain, was identified in a young Arabian filly with clinical signs similar to those of exertional rhabdomyolisis. However, this horse showed no changes in serum CK following exercise. A marked lactic acidosis developed even with light exercise, and maximum oxygen consumption was drastically reduced, resulting in marked exercise intolerance. Histopathologic evaluation of muscle biopsies showed an abnormal increase in mitochondrial density, and biochemical analyses revealed a Complex 1 deficiency. The horse has shown slowly progressive signs of muscle atrophy but has otherwise remained healthy at rest.

Glycogen Branching Enzyme Deficiency

Glycogen branching enzyme deficiency (GBED) is a glycogen storage disorder causing abortion, seizures, and muscle weakness in Quarter horse-related breeds caused by an autosomal recessive mutation in the glycogen branching enzyme (GBE1) gene. Nine percent of Quarter horses and Paint horses carry the mutation and at least 3% of abortions are attributed to this disease in Quarter horses. Most foals diagnosed with GBED present with hypothermia, weakness, and flexural deformities of all limbs at 1 day of age. Ventilatory failure may also be a presenting sign in addition to recurrent hypoglycemia and collapse. All foals have died either from euthanasia because of muscle weakness or suddenly because of apparent cardiac arrhythmia. Persistent leukopenia, intermittent hypoglycemia, and high serum CK (1,000–15,000 U/L), AST, and γ-glutamyltransferase activities are features of affected foals. Gross lesions are not evident, and routine H & E stains of tissues may be normal or show basophilic inclusions in skeletal muscle and cardiac tissues. Frozen sections of muscle, heart, and liver show a notable lack of normal PAS staining for glycogen as well as abnormal PAS-positive globular or crystalline intracellular inclusions. Branching enzyme activity is minimal in skeletal and cardiac muscle as well as liver. A diagnosis is best obtained by confirming the presence of the genetic mutation in tissue samples or by identifying typical PAS positive inclusions in muscle or cardiac samples. There is no successful treatment for GBED.

Last full review/revision March 2012 by Stephanie J. Valberg, DVM, PhD, DACVIM