Felipedia

Nemaline myopathy in cats

In people, nemaline myopathy is a disorder characterized morphologically by the presence of rods (nemaline bodies) in muscle cells. Various forms of the disease have been reported, including congenital, childhood-onset and adult-onset, and both autosomal dominant and autosomal recessive cases have been documented. Three genetic mutations have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3, the nebulin gene, and the actin gene. Nemaline myopathy appears to be most commonly associated with the autosomal recessive form caused by mutations in the nebulin gene. The pathogenesis of nemaline myopathy is still unclear although recent molecular genetic studies suggest that rod formation is secondary to contractile dysfunction [425]. The main component of the nemaline bodies is a-actinin.

Nemaline myopathy has been infrequently reported in animals. In 1986, Cooper and associates reported on nemaline myopathy in 5 cats, of either gender, derived from 4 litters from the same mother, thus suggesting possible autosomal recessive mode of inheritance. Clinical signs were observed in cats (a specific breed was not reported) between 6 months and 1.5 years of age. Cats appeared extremely apprehensive. Signs included mild weakness, reluctance to move, and a crouched, jerky hypermetric gait when prompted to move. Following a short period of movement, some cats appeared fatigued and panted. In some animals there was skin twitching and muscle atrophy (especially in scapular and gluteal muscles, and occasionally, in masticatory muscles). Patellar reflexes were consistently depressed or absent. Other spinal reflexes, along with sensation, were normal. Electrodiagnostic studies and cerebrospinal fluid analyses were normal, although mild increase in serum CK and lactate dehydrogenase levels were seen in some cats. Prognosis was poor. Clinical signs persisted for up to a year after signs first began, but did not appear to progress. However, muscle atrophy did progress, and cats became inappetent, lost condition, and were eventually euthanased.

Pathological findings were characterized by presence of large numbers of nemaline rods in skeletal muscle fibres (while all muscles examined were abnormal, the changes were most apparent in the proximal forelimb muscles), marked fibre size variation, atrophy of type 1 and type 2A fibres, internalised nuclei, and fibre splitting. In some muscles, core-like lesions were seen characterized by disorganization of the internal structure producing a swirling pattern and particularly evident on NADH-TR-stained myofibers. Rods stained red with trichrome stain and were aligned along the long axis of muscle fibres (in some instances measuring up to 5.7 mm in length). Rod numbers varied from a few to many (that filled some fibres) and were in subsarcolemmal or central locations. Rods were most common in atrophic type 1 and type 2A fibres. Predominance of type 1 fibres, typically a feature of the human disease, was not observed. Ultrastructurally, there was myofibrillar disarray. Rods were electron-dense and showed bi-directional periodicity (approximately 17 nm along the axis and 8 nm transversely) in longitudinal sections, and a lattice-like arrangement in cross-sections. Rods appeared to arise from Z-bands and the smallest rods consisted of localized expansions of the Z-band. No lesions were seen in extraneural tissues, brain, spinal cord, or peripheral nerves. Nemaline rods have been experimentally-induced in cats by tenotomy.