Predictive value of hypoglycin A and methylencyclopropylacetic acid conjugates in a horse with atypical myopathy in comparison to its cograzing partners

Abstract

Summary Hypoglycin A (HGA) was detected in blood and urine of a horse suffering from atypical myopathy (AM; Day 2, serum, 8290 μg/l; urine: Day 1, 574, Day 2, 742 μg/l) and in its cograzing partners with a high variability (46–1570 μg/l serum). Over the period of disease, the level of the toxic metabolites (methylencyclopropylacetic acid [MCPA]‐conjugates) increased in body fluids of the AM horse (MCPA‐carnitine: Day 2, 0.246, Day 3, 0.581 μmol/l serum; MCPA‐carnitine: Day 2, 0.621, Day 3, 0.884 μmol/mmol creatinine in urine) and HGA decreased rapidly (Day 3, 2430 μg/l serum). In cograzing horses MCPA‐conjugates were not detected. HGA in seeds ranged from 268 to 367 μg/g. Although HGA was present in body fluids of healthy cograzing horses, MCPA‐conjugates were not detectable, in contrast to the AM horse. Therefore, increasing concentrations of MCPA‐conjugates are supposed to be linked with the onset of AM and both parameters seem to indicate the clinical stage of disease. However, detection of HGA in body fluids of cograzing horses might be a promising step in preventing the disease.

Identification of hypoglycin A binding adsorbents as potential preventive measures in co‐grazers of atypical myopathy affected horses

“…HGA concentrations in all samples were determined by HPLC/electrospray negative ion tandem mass spectrometry. This method has recently been described for HGA analysis in AM affected horses . The initial mucosal concentration of HGA, HGA remaining on the mucosal side after 1 h of incubation and the serosal release of HGA were calculated using the HGA concentrations in the mucosal and the serosal compartments at 2 time points (T1 and T2) as well as the tissue concentrations after 75 min of incubation.…”

“…In horses with AM, acquired multiple acyl‐CoA dehydrogenase deficiency (MADD) results in inhibition of various mitochondrial enzymes leading to diminished β‐oxidation of fatty acids and accumulation of toxic acyl‐CoAs . Hypoglycin A (HGA) and its conjugated metabolites methylenecyclopropyl acetic acid (MCPA)‐carnitine and MCPA‐glycine have been identified in the bodily fluids of AM affected horses . Additionally, after Acer pseudoplatanus had been identified adjacent to pastures where cases of AM had occurred , HGA was also detected in sycamore seeds and samaras , and parts of the seeds have been identified in the stomach content of AM affected horses .…”

“…Although Koch's postulates have not yet been proven, the general consensus is that intestinal absorption of HGA followed by metabolism to MCPA‐conjugates is needed for the development of AM. In apparently healthy cograzing animals, serum concentrations of HGA and conjugated metabolites have been reported to be lower than in AM affected horses . Assuming the existence of subclinical cases of AM that may later develop clinical signs, preventative measures for cograzers should be implemented.…”

“…Currently there are no published data on the intestinal metabolism and absorption of HGA in horses. While factors determining whether cograzers develop AM are unknown , it appears crucial to minimise further absorption of HGA in these horses. The aim of the current study was to identify a therapeutic adsorbent capable of binding HGA and thereby effectively decreasing intestinal absorption of HGA.…”

Analysing hypoglycin A, methylenecyclopropylacetic acid conjugates and acylcarnitines in blood to confirm the diagnosis and improve our understanding of atypical myopathy

“…In their study, Bochnia et al . () suggest analysing HGA and MCPA‐conjugates in body fluids (i.e. serum and urine) of pasturing equids to indicate the clinical status regarding atypical myopathy: healthy vs. diseased animal.…”