Nemaline myopathy

From Felipedia

Nemaline rod myopathy, showing rod structures using modified Gomori trichrome stain

Nemaline rod myopathy is a rare genetic disease of cats which causes symptoms of myopathy. It appears to be an autosomal recessive disease, but autosomal dominant cases have been reorted.

There appears to be no breed or sex predisposition to this diseases, and signs are evident from 6 months of age, though some cats have been reported affected at 1.5 years of age^[1].

Cause

Nemaline rod myopathy is a disorder characterized by the presence of rods (nemaline bodies) in muscle cells. Various forms of the disease have been reported, including congenital, juvenile-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^[2]. The main component of the nemaline bodies is a-actinin^[3].

Clinical signs

Clinical signs are observed between 6 months and 1.5 years of age, including weakness, reluctance to move, and a crouched, jerky hypermetric gait when prompted to move. In some cats, skin twitching and muscle atrophy (especially in scapular and gluteal muscles, and occasionally, in masticatory muscles) occur. Patellar reflexes are often depressed or absent. Other spinal reflexes, along with sensation, are normal.

Electrodiagnostic studies and cerebrospinal fluid analyses are usually normal, although mild increase in serum CK and lactate dehydrogenase levels were seen in some cats^[4].

Diagnosis

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^[5].

This disease appears histologically similar to tubulin-reactive inclusion myopathy.

Treatment

Treatment for this disease is limited to palliative care. Euthanasia appears to be inevitable in most cases, although some cats appear to stabilise for various lengths of time before deteriorating.

References

1. ↑ Ruehlmann, DS (2010) Myopathic disorders. In August, JR (Ed): Consulations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia. pp:602
2. ↑ Gurgel-Giannetti J, Reed U, Bang ML, et al (2001) Nebulin expression in patients with nemaline myopathy. Neuromuscul Disord 11:154-162
3. ↑ Yamaguchi M, et al (1982) Nemaline myopathy rod bodies. Structure and composition. J Neurol Sci 56:35-56
4. ↑ Cooper BJ, et al (1986) Nemaline myopathy of cats. Muscle Nerve 9:618-625
5. ↑ Engel WK, Brooke MH, Nelson PG (1966) Histochemical studies of denervated or tenotomized cat muscle: illustrating difficulties in relating experimental animal conditions to human neuromuscular diseases. Ann N Y Acad Sci 138:160-185