South African Equine Veterinary Association Congress 2015 Protea Hotel Stellenbosch
Estimates of the prevalence of exercise-associated rhabdomyolysis in Thoroughbreds suggests
that 5- 7% of Thoroughbreds worldwide are affected (Cole et al. 2004; MacLeay et al.
1999a; McGowan et al. 2002), although it remains unknown whether all these animals have
the same disorder. Pedigree analysis of some lines of Thoroughbreds in the USA supports
autosomal dominant inheritance of the trait (Dranchak et al. 2005; MacLeay et al. 1999b).
Given that acquired forms of rhabdomyolysis are common in humans and other species it
seems possible, or likely that some Thoroughbreds develop acquired forms of the syndrome
as a result of some triggering environmental or management factor (MacLeay et al. 1999a).
Despite this, it is not possible to rule out a common underlying genetic predisposition within the
breed: it is well known that external factors modify the phenotype in many genetic
conditions. Furthermore, epidemiological evidence suggests that other breeds likely have the
same disorder (Standardbreds in particular) (Isgren et al. 2010).
The abnormality in muscle calcium regulation identified in some Thoroughbreds shares
certain experimental similarities to a condition recognised in humans and other species,
known as malignant hyperthermia (MH). In particular, muscle from horses with RER and
other species with MH is hypersensitive to agents (such as caffeine and halothane) that
stimulate release of calcium from the muscle calcium store (sarcoplasmic reticulum) through
a calcium release channel known as the ryanodine receptor (RYR1) (Bendahan et al. 2004;
Lentz et al. 1999; Lentz et al. 2002). However, though MH has been reported in some
horses following halothane anaesthesia, and indeed, though an RYR1 receptor mutation has
been identified in MH-susceptible Quarter horses (Aleman et al. 2004), Thoroughbreds with
abnormal calcium regulation do not share the same mutation and there is evidence suggesting
that the RYR1 receptor is not involved in Thoroughbred RER (Dranchak et al. 2004). Given
that inhalational anaesthesia is common in equine veterinary work, but MH-like episodes are
extremely rare, and certainly more scarce than ER, this seems unsurprising. Despite this, some
basic research similarities between RER and MH do still suggest the possibility of
involvement of another protein or proteins that regulate intracellular calcium concentration in
muscle although this is not supported by recent evidence from my group. The search for a gene
or genes mutated in Thoroughbreds continues.
Polysaccharide Storage Myopathy types 1 & 2
Polysaccharide storage myopathy (PSSM or EPSM) can be definitively diagnosed by muscle
biopsy. Pathognomonic changes include amylase-resistant inclusions detected by Periodic
Acid Schiff staining. Horses with this disorder are hypersensitive to insulin and clear glucose
from the circulation more rapidly than normal animals (Annandale et al. 2004). This disease
was first reported in detail in Quarter Horses with exertional rhabdomyolysis in the USA
(Valberg et al. 1992). Since then, a disease with similar, if not identical histopathological
features has been reported in a variety of other breeds, in particular draught horses ((McCue et
al. 2006; Valentine et al. 1997; Valentine et al. 2001)} in several countries, including the
UK (McGowan et al. 2003). The Comparative Neuromuscular Diseases Laboratory at the
Royal Veterinary College has since diagnosed this condition in a number of breeds, including
ponies, cobs and Connemaras (Stanley et al. 2009). (Although there are sometimes clinical
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