Equine Multiple Acyl‐CoA Dehydrogenase Deficiency (MADD) Associated with Seasonal Pasture Myopathy in the Midwestern United States

Abstract

Background: Seasonal pasture myopathy (SPM) is a highly fatal form of nonexertional rhabdomyolysis that occurs in pastured horses in the United States during autumn or spring. In Europe, a similar condition, atypical myopathy (AM), is common. Recently, a defect of lipid metabolism, multiple acyl-CoA dehydrogenase deficiency (MADD), has been identified in horses with AM.Objective: To determine if SPM in the United States is caused by MADD. Animals: Six horses diagnosed with SPM based on history, clinical signs, and serum creatine kinase activity, or postmortem findings.Methods: Retrospective descriptive study. Submissions to the Neuromuscular Diagnostic Laboratory at the University of Minnesota were reviewed between April 2009 and January 2010 to identify cases of SPM. Inclusion criteria were pastured, presenting with acute nonexertional rhabdomyolysis, and serum, urine, or muscle samples available for analysis. Horses were evaluated for MADD by urine organic acids, serum acylcarnitines, muscle carnitine, or histopathology.Results: Six horses had clinical signs and, where performed (4/6 horses), postmortem findings consistent with SPM. Affected muscle (4/4) showed degeneration with intramyofiber lipid accumulation, decreased free carnitine concentration, and increased carnitine esters. Serum acylcarnitine profiles (3/3) showed increases in short-and medium-chain acylcarnitines and urinary organic acid profiles (3/3) revealed increased ethylmalonic and methylsuccinic acid levels, and glycine conjugates, consistent with equine MADD.Conclusions and Clinical Importance: Similar to AM, the biochemical defect causing SPM is MADD, which causes defective muscular lipid metabolism and excessive myofiber lipid content. Diagnosis can be made by assessing serum acylcarnitine and urine organic acid profiles.

Metabolic features of chronic fatigue syndrome

“…FAD is an important cofactor for fatty acid oxidation and sterol synthesis and is required for activation and oxidation of vitamin B6 (pyridoxine); lipoic acid metabolism (E3 subunit) needed for pyruvate, alpha-ketoglutarate, and branched chain amino acid oxidation; vitamin A activation; 5-methyltetrahydrofolic acid synthesis; niacin and NAD synthesis; and glutathione reduction. Functional deficiency of riboflavin can be produced by dietary and environmental factors (21). Severe riboflavin deficiency can present with a plasma acyl-carnitine pattern similar to multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric aciduria type II (GAII) (22).…”

Atypical myopathy: an update

“…In 2006, a similar condition called seasonal pasture myopathy was recognised in the USA (Finno and others 2006); cases also exhibited a MADD-like biochemical profile (Sponseller and others 2012). Following a botanical survey, it was hypothesised that the condition was caused by ingestion of seeds from Acer negundo (box elder tree) (Fig 5) as these trees were present on all pastures associated with cases.…”

The Story of Equine Atypical Myopathy: A Review from the Beginning to a Possible End

“…It is now believed that SPM is indeed similar to AM as it has been showed that biochemical defects of both syndromes are identical [23, 24]. Cases compatible with a diagnosis of AM also have been reported from Australia [25] and New Zealand (information from AMAG).…”

“…Horses with AM show hyperglycemia [3, 10, 12, 16, 23, 24] and increased free serum carnitine levels [24], although a decrease in muscle free carnitine has been found [23], whereas humans with MADD have hypoglycemia and decreased free carnitine levels. These differences are possibly explained by species-specific steps in energy metabolism.…”

“…The studies of Westermann et al [24] demonstrated no significant increase in plasma and muscular long-chain acylcarnitines in affected horses (no or only very mild increases), and they only tested the muscle activity of short- and medium-chain acyl-CoA dehydrogenases, not of long-chain acyl-CoA dehydrogenases [24, 39]. More recently, cases have been noted to have significant elevations of long-chain acylcarnitines ([23]; unpublished results Votion et al), suggesting also a deficiency in long-chain acyl-CoA dehydrogenases.…”