Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

IX. Selected Neuromuscular Disorders of Domestic Animals
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of muscle in which there is a marked increase in serum
CK and AST enzyme activities, gross hypertrophy of some
muscle groups, and weakness and atrophy of other muscles
in dogs and cats. Affected individuals may also have a cardiomyopathy,
as the dystrophin deficiency also involves
cardiac myofibers ( Moise et al. , 1991 ). In dogs, the onset
of clinical signs is usually evident by 2 to 4 months of age
and somewhat later in cats. In dogs, this disorder was first
observed in golden retrievers and has subsequently been
identified in other breeds, including Irish terriers, rottweilers,
German short-haired pointers, and Samoyeds.
Histological sections reveal focal lesions consisting of
myofiber clusters undergoing the spectrum of change from
myonecrosis through macrophage infiltration and phagocytosis
to regeneration. Individual fibers may be atrophic or
hypertrophic, calcified, and hypercontracted, and may possess
central nuclei. Beyond clinical signs and biopsy features,
immunoblotting and immunocytochemical staining
for dystrophin within muscle biopsies and genetic screening
are valuable diagnostic methods for detecting dystrophin
deficiency.
C . Immune-Mediated Canine Masticatory
Muscle Myositis
The muscles of mastication are selectively affected in an
inflammatory muscle disorder in dogs known as masticatory
muscle myositis ( Evans et al. , 2004 ). Limb muscles are
essentially spared. The muscles of mastication in the dog
are principally composed of type 2 m myofibers, fast-twitch
fibers that possess a unique isoform of myosin, heavy and
light chains ( Shelton et al. , 1985 ). This disorder appears to
be an MHC-1-restricted CD8( ) T-cell-mediated autoimmune
disease ( Shelton and Paciello, 2006 ). Dogs afflicted
with this disorder produce autoantibodies directed against
type 2 m fibers LC2-M (myosin light chain 2-masticatory),
which has little cross-reaction with type 2a fibers of limb
muscles. Diagnosis of the disorder includes muscle biopsy
demonstration of lymphocytic and plasmocytic cellular infiltrates
around muscle fibers and in perivascular locations.
Occasionally eosinophils are present as the predominant
infiltrate. In chronic cases, muscle atrophy and fibrosis are
apparent. Localization of immunoglobulins fixed to type 2 m
fibers within the biopsy and demonstration of circulating
antibodies against type 2 m fibers employing SPA-HRP are
more specific diagnostic tests ( Shelton et al. , 1987 ).
D . Disorders of Glyco(geno)lysis Affecting
Skeletal Muscle
Disorders of glyco(geno)lysis affecting skeletal muscles
variably involve some excess storage of glycogen within
affected myofibers, resulting in the presence of glycogencontaining
vacuoles. In humans, glycogen storage diseases
(GSD) affecting muscle include deficiencies of α-l, 4-
glucosidase (GSD-II), debranching enzyme (GSD-III),
branching enzyme (GSD-IV), myophosphorylase (GSD-V),
phosphofructokinase (GSDVII), phosphorylase b kinase
(VIII), phosphoglycerate kinase (GSD-IX), phosphoglycerate
mutase (GSD-X), and lactate dehydrogenase (XI)
( Tsujino et al. , 2000 ). Though variably documented, some
of these disorders also occur in domestic animals.
1 . α -1,4-Glucosidase Defi ciency (GSD II)
Lysosomal α -1,4-glucosidase deficiency, also known as
Pompe’s disease, generalized type II glycogenosis, and acid
maltase deficiency, occurs in humans with childhood (infantile
and juvenile) and adult forms, which are variations of
the same disorder based on the age of onset and tissue and
organ involvement ( Reuser et al. , 1995 ). This disorder is
inherited as an autosomal recessive trait. This disorder has
also been reported in shorthorn and Brahman cattle ( Dennis
et al. , 2000 ). Both infantile and late-onset equivalent variations
have been described ( Dorling et al. , 1981 ; Howell
et al. , 1981 ). Clinical signs in Brahman calves become evident
at 2 to 3 months of age with a loss of condition, poor
growth, and lethargy followed by incoordination and muscle
tremors with death by 9 months of age. Although the onset of
clinical signs may also occur within the first 2 to 3 months of
age, some affected shorthorn calves appear clinically normal
until 5 to 9 months of age when weight gains are not maintained
and progressive muscular weakness develops with
death by 12 to 16 months of age. Excessive accumulation of
glycogen occurs in skeletal and cardiac muscle, brain, and
spinal cord ( Howell et al. , 1981 ). The disorder in cattle is
also inherited as an autosomal recessive trait. Two mutations
have been identified in Brahmans, and one in shorthorns,
that lead to generalized glycogenosis. All three mutations
result in premature termination of translation ( Dennis et al. ,
2000 ). In other species, single cases of generalized glycogenoses
in which α -glucosidase deficiency was demonstrated
include the Lapland dog ( Walvoort et al. , 1982 ) and
Japanese quail ( Murakami et al. , 1980 ).
2 . Debranching Enzyme Defi ciency (GSD III)
Debranching enzyme possesses two activities, α-l,4glucan
transferase and α -l,6-glucosidase. In the hydrolysis of glycogen,
myophosphorylase acts on the α -l,4 linkages of the
terminal glucose residues up to the last four glucose residues
preceding the α -1,4 linkages. The α-l,4-glucan transferase
transfers the last three residues to another branch and
the α -1,6-glucosidase hydrolyses the α -l,6 branch point.
Several presumed cases of debranching enzyme deficiency
have been described in the dog ( Ceh et al. , 1976 ; Otani and
Mochizuki, 1977 ; Rafiquzzaman et al. , 1976 ). Biochemical
demonstration of debranching enzyme deficiency is limited
to a single case ( Ceh et al. , 1976 ). There is diffuse organ
involvement with glycogen storage. Onset of signs appears