Equine biochemical multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause of rhabdomyolysis.

This research article discusses the detection of multiple acyl-CoA dehydrogenase deficiency (MADD), a biochemical disorder, in two horses, marking the first time the condition has been identified in animals. This deficiency was discovered in the course of diagnosing the horses with rhabdomyolysis, a condition characterized by the rapid breakdown of damaged skeletal muscle.

Introduction to the Research

This research focuses on a medical discovery involving two horses: a 7-year-old Groninger warmblood gelding and a six-month-old Trakehner mare. These horses were initially presented with symptoms of rhabdomyolysis – a condition involving the rapid breakdown and death of muscle, which can lead to severe kidney damage. Through further examination, the horses were also found to exhibit a genetic disorder called multiple acyl-CoA dehydrogenase deficiency (MADD), marking the first occurrence of this disorder being diagnosed in animals.

Diagnosis and Symptoms

• The horses’ symptoms included a stiff, unsure gait, excess muscle breakdown, and finally, lying prone without being able to rise.
• Clinical examination and testing revealed various abnormalities in their urine, blood plasma, and muscle tissues.
• Tests on their blood plasma showed heightened glucose levels (hyperglycemia), elevated lactic acid levels (lactic acidemia), increased activity of muscle enzymes (ASAT, LDH, CK) and impaired kidney function (increased urea and creatinine levels).

Biochemical Discoveries

Acyl-CoA dehydrogenase is a key enzyme involved in the breaking down of fatty acids in the body. When there’s a deficiency of this enzyme, it can result in a buildup of fatty acids, leading to multiple health problems, such as rhabdomyolysis as seen in these horses. More in-depth investigation of these horses’ conditions showed:

• Elevated levels of several organic acids in the urine, including lactic acid, ethylmalonic acid (EMA), 2-methylsuccinic acid, butyrylglycine, (iso)valerylglycine and hexanoylglycine. EMA was also found in high levels in the blood plasma of the horses.
• The acylcarnitines (a type of molecule that helps transport fatty acids into mitochondria, where they are broken down for energy) in the horses’ blood plasma were found to be excessively high. This was also the case in their urine.

Indications of MADD

• A hypofunctioning of several enzymes including short-chain acyl-CoA dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and isovaleryl-CoA dehydrogenase (IVD) was discovered in muscle tissue.
• This result, paired with the other findings, indicated the presence of MADD in these horses — a revelation that marks a first in equine medicine.
• MADD in humans is typically considered a genetic disorder, but given the normal activities of specific other enzymes (ETF and ETF-QO) in these horses, the researchers suggest that their MADD is an acquired, rather than inherited, disorder.