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Introduction: Recessive mutations in the anoctamin-5 gene (ANO5) cause a spectrum of clinical phenotypes, including limb-girdle muscular dystrophy (LGMD 2L), distal myopathy, and asymptomatic hyperCKemia., Methods: In this report we describe our clinical, electrophysiological, pathological, and molecular findings in a subject with anoctaminopathy-5., Results: A 49-year-old Arabic man from a consanguineous family presented with a 5-year history of myalgias, hyperCKemia and an episode of unprovoked rhabdomyolysis. Muscle biopsy showed mild myopathic changes and interstitial amyloid deposition. ANO5 analysis detected a novel homozygous deletion of approximately 11.9 kb encompassing exons 13-17, predicted to be pathogenic., Conclusions: Anoctaminopathy-5 can manifest with a phenotype reminiscent of metabolic myopathy and should be considered as a potential cause of myalgia and myoglobinuria. Amyloid deposition in the muscle biopsy is helpful for the diagnosis. A novel homozygous ANO5 deletion was identified, suggesting that screening for common mutations may have low yield in non-European subjects., (Copyright © 2014 Wiley Periodicals, Inc.)

To clarify the involvement of calpains in sarcolemmal remodeling, we examined the expression of calpains and their substrate, alpha-fodrin, in various disorders of muscle. Although immunohistological reactions for alpha-fodrin and calpains were weak in normal control muscles, intense immunoreactivity for alpha-fodrin at the sarcolemma and for calpains throughout the cytoplasm were detected in small muscle fibers from patients with inflammatory myositis (IM), rhabdomyolysis (Rhab), and Duchenne muscular dystrophy (DMD). Most of the calpain-alpha-fodrin double-positive muscle fibers in IM and Rhab also expressed the developmental form of myosin heavy chain. The sarcolemma of these small muscle fibers reacted with an antibody that specifically recognizes the 150-kDa fragments of alpha-fodrin (SBDP 150s) cleaved by calpain, but not caspase 3. Western blot analysis confirmed these results. These observations indicate that calpain is activated and reacts with alpha-fodrin as a substrate at the sarcolemma, and plays a key role in modulating sarcolemmal proteins to adapt to the specific conditions in each myopathy.

Skeletal muscle involvement can occur at all stages of human immunodeficiency virus (HIV) infection, and may represent the first manifestation of the disease. Myopathies in HIV-infected patients are classified as follows: (1) HIV-associated myopathies and related conditions, including HIV polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitic processes, myasthenic syndromes, and chronic fatigue; (2) muscle complications of antiretroviral therapy, including zidovudine and toxic mitochondrial myopathies related to other nucleoside-analogue reverse-transcriptase inhibitors (NRTIs), HIV-associated lipodystrophy syndrome, and immune restoration syndrome related to highly active antiretroviral therapy (HAART); (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. Introduction of HAART has dramatically modified the natural history of HIV disease by controlling viral replication, but, in turn, lengthening of the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions.

We report the case of a 79-year-old man with mild chronic renal failure who developed severe rhabdomyolysis after combined exposure to simvastatin and colchicine. Colchicine induces myopathy through disruption of microtubular function with subsequent vacuolization and pseudomyelinic body accumulation. Statin therapy is associated with myonecrosis, membranous myeloid bodies, and vacuolization, presumably as a function of impaired isoprenoid metabolism. Vesicle trafficking requires small G-protein prenylation and statins can disrupt cytoskeletal integrity. We propose that synergistic cytoskeletal myotoxicity may account for the extreme elevation of serum creatine kinase not previously reported in pure colchicine myopathy.

Oxidative stress has been implicated in the pathogenesis of several muscle diseases. Semicarbazide-sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines. In the oxidative reactions, amine substrates are converted into the aldehyde, followed by the production of ammonia and H(2)O(2). Although normal levels in muscle are very low, SSAO is expressed in almost all mammalian tissues. In this study, we examined the possible implication of SSAO as an additional source of oxidative stress in the pathogenesis of muscle disorders. The expression of SSAO was examined immunohistochemically in muscle biopsy specimens from patients with inclusion-body myositis (IBM; n = 5), desmin-related myopathy (DRM; n = 3), dermatomyositis (n = 3), granulomatous (sarcoid) myopathy (n = 2), muscle denervation-reinnervation (n = 3), and rhabdomyolysis (n = 2), as well as from control subjects (n = 3). Strong SSAO immunoreactivity was present in vacuolated and nonvacuolated fibers in IBM, in abnormal fibers in DRM, and in degenerating and regenerating fibers in dermatomyositis and rhabdomyolysis. In addition, SSAO overexpression was observed in muscle fibers adjacent to granulomas in sarcoid myopathy. These results suggest that SSAO is a source of oxidative stress in diseased human skeletal muscle and that it contributes to oxidative stress-induced damage in various inflammatory and other myopathies. Alternatively, the expression of SSAO in muscle fibers may be a consequence of muscle fiber injury.

A 43-year-old woman was admitted with progressive leg pains and weakness and was found to have rhabdomyolysis. Prior to this admission the patient had hypercalcemia, but this returned to normal following treatment with calcitonin. During the hospitalization, she developed the syndrome of calciphylaxis consisting of necrotic skin and muscle associated with vascular calcification. This is the first case report of rhabdomyolysis caused by calciphylaxis in a patient without chronic renal failure., (Copyright 2000 John Wiley & Sons, Inc.)

A Charolais calf presented to the Veterinary Medical Teaching Hospital with a history of recumbency following forced exercise. The calf was unable to stand, and had severe rhabdomyolysis, dehydration, and electrolyte imbalance. Blood selenium concentrations were within normal limits. A complete absence of histochemical staining for phosphorylase was apparent in muscle biopsies. Five other animals in the herd also had exercise intolerance and had a complete absence of phosphorylase staining in muscle biopsies. Biochemical analyses confirmed a deficiency of myophosphorylase (range 0-0.3 mumol/g per minute: normals 15-27) with normal to slightly elevated muscle glycogen concentrations. Pedigrees from all affected animals showed a common ancestor on the sire's and dam's side of each phosphorylase-deficient animal, suggesting an autosomal recessive transmission. Although myophosphorylase deficiency was described in humans (McArdle's disease) over 40 years ago, these cattle represent the first animal model for this disease.

The histochemical features of muscle injury and repair were examined in an experimental form of acute alcoholic myopathy in the rat. Typical features of rhabdomyolysis were found, which were indicated by scattered muscle fiber necrosis followed by sequential phases of fiber degeneration, phagocytosis, and regeneration. Nests of small, regenerated, or split fibers remained 2 months after the episode of acute myopathy. Vulnerability of type 1 fibers to alcohol-induced muscle injury was evident by selective involvement of muscles with type 1 fiber predominance and by the fact that regenerating fibers were virtually exclusively type 1. The histologic features of myopathy in this model closely parallel those in human acute alcoholic myopathy.