Proximal Limb Muscle Weakness Research Articles

Myofibrillar myopathies

The aim of this communication is to provide an up-to-date overview of myofibrillar myopathies. The most important recent advance in the myofibrillar myopathies has been the discovery that mutations in Z band alternatively spliced PDZ-containing protein and filamin C, as well as in desmin, alphaB-crystallin and myotilin, result in similar pathologic alterations in skeletal muscle that are typical of myofibrillar myopathy. Despite the increasing genetic heterogeneity, the clinical and morphologic phenotypes are remarkably homogeneous. The typical clinical manifestation is slowly progressive proximal, distal or both proximal and distal limb muscle weakness. Cardiomyopathy can be associated and is sometimes the presenting finding. Peripheral neuropathy also occurs in some patients. In every myofibrillar myopathy, there is abnormal accumulation of an array of proteins at ectopic sites as well as accumulation of degraded myofibrillar proteins forming large aggregates. The key issue now is to analyze the molecular mechanisms underlying the cascade of events that destroy the myofibrillar architecture and trigger the aberrant expression of multiple proteins. Several disease genes have recently been recognized in myofibrillar myopathies. So far, the disease proteins identified are components of or chaperone for the Z-disk. In each case, the molecular defect leads to a stereotyped cascade of structural events in the muscle fiber.

HLA associations with inclusion body myositis.

Inclusion body myositis (IBM) is defined clinically by a characteristic pattern of progressive proximal and distal limb muscle weakness and resistance to steroid therapy, and histologically by the presence of distinctive rimmed vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which CD8+ T cells are predominant. Muscle damage is believed to be mediated by autoimmune mechanisms, but very little information is available on the immunogenic features of IBM. MHC class I and DR antigens were typed on 13 caucasoid patients with IBM using standard serological techniques or by allele-specific oligonucleotide typing. Complement components C4 and properdin factor B (Bf) were typed by immunofixation after electrophoresis. Restriction fragment length polymorphisms (RFLP) in the class III region were analysed using cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data were examined for likely haplotypes by considering together the alleles at the class I, DR and complement loci along with the C4 and CYP21 RFLP. Ten of the DR3+ subjects had a 6.4-kb C4-hybridizing fragment characteristic of a deletion of C4A and CYP21-A. These patients probably carried all, or at least the class II and III regions, of the extended haplotype marked by B8/C4A*Q0/C4B1/BfS/DR3/DR52, which has been associated with several autoimmune diseases and is present in 11% of the healthy caucasoid population. Of the remaining subjects, two had evidence of the extended haplotype marked by B18/C4A3/C4BW*0/BfF1/DR3, which is present in less than 5% of the healthy population and has been associated with insulin-dependent diabetes mellitus. These data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.

Epilepsia partialis continua in mitochondrial dysfunction: Interesting phenotypic and MRI observations

An 11-year-old girl manifested with photophobia, ptosis, external ophthalmoplegia, hypotonia, weakness of proximal limb muscles, hyporeflexia, and generalized seizures (six months). Her elder sister had had uncontrolled seizures and photophobia and died at seven years of age. In the patient, serum lactate was high (55 mg/dl). Muscle biopsy revealed characteristic ragged red and ragged blue fibers, diagnostic of mitochondrial cytopathy. Sequencing of the complete mitochondrial genome of the DNA obtained from the muscle biopsy of the patient did not show any characteristic mutation. Four months later, the girl was admitted with a one-week history of epilepsia partialis continua (EPC). EEG revealed Periodic Lateralized Epileptiform Discharges (PLEDs), once in 2-4 seconds, over the right temporo-occipital leads. MRI revealed signal change of right motor cortex, which had restricted diffusion. MR spectroscopy (MRS) from this region revealed lactate peak. EPC remained refractory to multiple anti-epileptic drugs, immuno-modulators, coenzyme-Q, and carnitine. This thought provoking report expands the spectrum of mitochondrial cytopathies.

PTOSIS AS A FEATURE OF LATE-ONSET GLYCOGENOSIS TYPE II

Groen et al.1 describe unilateral myogenic ptosis in 4/12 (33%) adults with type II glycogenosis. Ptosis was the presenting symptom in three out of four patients suggesting that it may help in the early diagnosis of the disease. We describe a woman with genetically defined type II glycogenosis in whom ptosis preceded by 2 years the development of skeletal muscle weakness. Our patient developed unilateral ptosis at 46 years of age, when the only muscle symptom was abnormal fatigability during stair climbing. At 48, she began to complain of walking difficulties. Neurologic examination showed proximal lower limb muscle weakness (4/5 on MRC score), unilateral ptosis, and raised CK levels (220 U/L, normal 24 …

A large german kindred with cold‐aggravated myotonia and a heterozygous A1481D mutation in the SCN4A gene

Muscle sodium-channel disorders cover a spectrum of rare myotonic diseases. In a German family with 17 affected individuals in four generations, we identified a heterozygous missense mutation in exon 24 A1481D (c.4442 C>A) of the voltage-gated sodium channel gene (SCN4A) alpha subunit. Phenotypes of 12 family members were characterized by a mild myotonia with cold sensitivity but without paramyotonia. The index patient presented with fluctuating cold- and exercise-induced stiffness of ocular, facial, and distal muscles. The myotonia became more severe at the age of 22 years. His father had had cold- and exercise-induced periodic weakness with fluctuating myotonia since age 10. Later he developed a more severe, purely exercise- and cold-aggravated myotonia of arms, hands, and facial muscles. The father's mother presented with cold-induced myotonia until age 65, when progressive weakness of proximal limb muscles developed. Her muscle biopsies revealed considerable myopathic changes with a variety of fine structural alterations. This study presents a family with cold-aggravated myotonia and progression of myopathic changes in the muscle biopsy with increasing age. In older patients, sodium channelopathies may mimic the phenotypic features of myotonic dystrophy type 2.

Ptosis as a feature of late-onset glycogenosis type II

Groen et al.1 describe unilateral myogenic ptosis in 4/12 (33%) adults with type II glycogenosis. Ptosis was the presenting symptom in three out of four patients suggesting that it may help in the early diagnosis of the disease. We describe a woman with genetically defined type II glycogenosis in whom ptosis preceded by 2 years the development of skeletal muscle weakness. Our patient developed unilateral ptosis at 46 years of age, when the only muscle symptom was abnormal fatigability during stair climbing. At 48, she began to complain of walking difficulties. Neurologic examination showed proximal lower limb muscle weakness (4/5 on MRC score), unilateral ptosis, and raised CK levels (220 U/L, normal 24 …

Effect of oculopharyngeal muscular dystrophy‐associated extension of seven alanines on the fibrillation properties of the N‐terminal domain of PABPN1

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that usually manifests itself within the fifth decade. The most prominent symptoms are progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is caused by trinucleotide (GCG) expansions in the N-terminal part of the poly(A)-binding protein 1 (PABPN1) that result in the extension of a 10-alanine segment by up to seven more alanines. In patients, biopsy material displays intranuclear inclusions consisting primarily of PABPN1. Poly l-alanine-dependent fibril formation was studied using the recombinant N-terminal domain of PABPN1. In the case of the protein fragment with the expanded poly l-alanine sequence [N-(+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils serving as seeds. Besides homologous seeds, seeds derived from fibrils of the wild-type fragment (N-WT) also accelerated fibril formation of N-(+7)Ala in a concentration-dependent manner. Seed-induced fibrillation of N-WT was considerably slower than that of N-(+7)Ala. Using atomic force microscopy, differences in fibril morphologies between N-WT and N-(+7)Ala were detected. Furthermore, fibrils of N-WT showed a lower resistance against solubilization with the chaotropic agent guanidinium thiocyanate than those from N-(+7)Ala. Our data clearly reveal biophysical differences between fibrils of the two variants that are likely caused by divergent fibril structures.

A Drosophila model of oculopharyngeal muscular dystrophy reveals intrinsic toxicity of PABPN1

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset syndrome characterized by progressive degeneration of particular muscles. OPMD is caused by short GCG repeat expansions within the gene encoding the nuclear poly(A)-binding protein 1 (PABPN1) that extend an N-terminal polyalanine tract in the protein. Mutant PABPN1 aggregates as nuclear inclusions in OMPD patient muscles. We have created a Drosophila model of OPMD that recapitulates the features of the human disorder: progressive muscle degeneration, with muscle defects proportional to the number of alanines in the tract, and formation of PABPN1 nuclear inclusions. Strikingly, the polyalanine tract is not absolutely required for muscle degeneration, whereas another domain of PABPN1, the RNA-binding domain and its function in RNA binding are required. This demonstrates that OPMD does not result from polyalanine toxicity, but from an intrinsic property of PABPN1. We also identify several suppressors of the OPMD phenotype. This establishes our OPMD Drosophila model as a powerful in vivo test to understand the disease process and develop novel therapeutic strategies.

The Impact of Overt and Subclinical Hyperthyroidism on Skeletal Muscle

Patients with overt hyperthyroidism (OH) commonly have proximal limb muscle weakness that improves after correction of hyperthyroidism. It is unclear, however, if patients with milder degrees of hyperthyroidism (referred to as subclinical hyperthyroidism or SCH) may also have a degree of muscle weakness. This may have clinical relevance as SCH patients are often elderly and may therefore have concurrent sarcopenia of aging and would represent a previously unrecognized complication of SCH. We measured both thigh strength and cross-sectional area in patients with OH (n = 30) or SCH (n = 24), both prior to treatment of hyperthyroidism and again at 6-9 months after the restoration of a euthyroid state. Euthyroid controls (n = 48) were studied at similar time intervals. Prior to treatment, both knee flexor and extensor muscle strength was reduced in both patients with OH and SCH compared to controls (p < 0.05). After treatment all strength measurements improved in the OH group (p < 0.01) while in the SCH group the majority of muscle strength measurements improved (p < 0.05). Midthigh muscle cross-sectional area was reduced in both the OH and SCH group at baseline (p < 0.05) compared to controls and increased significantly following treatment (p < 0.05). There were no significant changes in any parameter in the euthyroid control (EC) group during the study period. The finding that muscle strength and cross-sectional area are reduced in SCH and improved after treatment lends support for the clinical decision to treat rather than observe this condition. This may have particular relevance to certain SCH patient groups including the elderly who are prone to falls and athletically active younger patients who require optimal skeletal muscle function.

Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation mimicking a myopathy

A 71-year-old woman with a family history of amyotrophic lateral sclerosis (ALS) was investigated for symmetrical, proximal limb and abdominal muscle weakness. Initial examination showed mild proximal muscle weakness in the arms and legs, slightly elevated serum creatine kinase (CK) level, and normal electromyographic (EMG) findings. A myopathy was the presumed diagnosis. Over the next year, weakness became severe and tendon reflexes became unelicitable; no upper motor signs were present. EMG then showed acute and chronic denervation and a muscle biopsy showed target fibers and grouped atrophy. DNA analysis revealed a G72C CuZn-superoxide dismutase (SOD1) mutation. Fasciculations were absent throughout the disease. The patient died 53 months after symptom onset and autopsy revealed loss of lower motor neurons (LMN) and SOD1-positive inclusions. This case expands the phenotypic spectrum of ALS associated with SOD1 mutations to include presenting features that mimic a myopathy.

Organophosphate-Induced Intermediate Syndrome

The intermediate syndrome (IMS) following organophosphorus (OP) insecticide poisoning was first described in the mid-1980s. The syndrome described comprised characteristic symptoms and signs occurring after apparent recovery from the acute cholinergic syndrome. As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'. The IMS occurs in approximately 20% of patients following oral exposure to OP pesticides, with no clear association between the particular OP pesticide involved and the development of the syndrome. It usually becomes established 2-4 days after exposure when the symptoms and signs of the acute cholinergic syndrome (e.g. muscle fasciculations, muscarinic signs) are no longer obvious. The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. Thus, some patients may only have weakness of neck muscles whilst others may have weakness of neck muscles and proximal limb muscles. These patients may not require ventilatory care but close observation and monitoring of respiratory function is mandatory. Management is essentially that of rapidly developing respiratory distress and respiratory failure. Delays in instituting ventilatory care will result in death. Initiation of ventilatory care and maintenance of ventilatory care often requires minimal doses of non-depolarising muscle relaxants. The use of depolarising muscle relaxants such as suxamethonium is contraindicated in OP poisoning. The duration of ventilatory care required by patients may differ considerably and it is usual for patients to need ventilatory support for 7-15 days and even up to 21 days. Weaning from ventilatory care is best carried out in stages, with provision of continuous positive airway pressure prior to complete weaning. Continuous and close monitoring of respiratory function (arterial oxygen saturation, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood) and acid-base status are an absolute necessity. Prophylactic antibiotics are usually not required unless there has been evidence of aspiration of material into the lungs. Close monitoring of fluid and electrolyte balance is mandatory in view of the profuse offensive diarrhoea that most patients develop. Maintenance of nutrition, physiotherapy, prevention of bed sores and other routine measures to minimise discomfort during ventilatory care are necessary. Recovery from the intermediate syndrome is normally complete and without any sequelae. The usefulness of oximes during the IMS remains uncertain. In animal experiments, very early administration of oximes has prevented the occurrence of myopathy. There are reports from developed countries where administration of oximes at recommended doses and within 2 hours of ingestion of OP insecticide did not prevent the onset of the IMS. Controlled randomised clinical studies are necessary to evaluate the efficacy of oximes in combating the IMS. Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Of these, the decrementing response is the most frequent finding during the IMS, whilst repetitive firing is observed during the acute cholinergic syndrome. The distribution of the weakness in human cases of the IMS, in general, parallels the distribution of the myopathy observed in a number of studies in experimental animals. This has led to speculation that myopathy is involved in the causation of the IMS. However, while myopathy and the IMS have a common origin in acetylcholine accumulation, they are not causally related to one another.

A Case of Intermediate Syndrome of Organophosphate Poisoning after Dermal Exposure

Background: Organophosphate poisoning is one of the most common toxicologic emergencies in Korea. Acute organophosphate poisoning and delayed polyneuropathy by ingestion are well published. There have been several reports about intermediate syndrome in organophosphate poisoning by ingestion but few about intermediate syndrome via dermal route. Case report: We observed a 59-years-old male who had weakness of proximal limb muscles and respiratory muscles 2 days after dermal exposure by unidentified pesticide. The paralytic symptoms lasted up to 20 days but the delayed polyneuropathy did not develop. The patient needed mechanical ventilatory support for 2 weeks and had completely recovered from IMS 6 weeks later. Electrophysiological study was characterized by an axonal polyneuropathy pattern on the proximal limb muscles. Serum acetylcholinesterase level was below half of normal level. Clinical manifestations and electrophysiological study support the clinical diagnosis of intermediate syndrome. C o n c l u s i o n: Intermediate syndrome is commonly developed by ingestion of organophosphate but, as in this case, dermal absorption can also lead to intermediate syndrome. More detailed history taking and close observation is needed for about 3 or more days after intoxication because of the risk of respiratory failure.

Oculopharyngeal muscular dystrophy in Hispanic New Mexicans.

Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy caused by polyalanine triplet repeat expansion in the gene for poly(A) binding protein 2 (PABP2) and is found in isolated cohorts throughout the world. We have observed numerous cases of OPMD in New Mexico. To characterize the clinical, genetic, and demographic features of the OPMD population in New Mexico. Cohort study with analysis of outpatient clinic medical records from 1965 to 2001 at the University of New Mexico Hospital and the New Mexico VA Health Care System in Albuquerque, which serve the entire state. Clinical phenotype, supplemented with genetic confirmation (n = 10 patients) and in-depth clinical evaluations (n = 49 patients). We identified 216 cases of OPMD (99 women and 117 men) from 39 kindreds of New Mexicans spanning up to 4 generations. All patients were Hispanic, and the majority of probands came from northern New Mexico. In patients who had both ocular and pharyngeal muscle weakness, ptosis was just as likely to occur before or concurrent with dysphagia. Proximal limb muscle weakness and gait abnormalities were common and occurred later than ocular or pharyngeal weakness. The clinical expression of OPMD caused marked debility, although life-table analysis showed no decrease in life expectancy compared with unaffected family members (P =.81). Ten individuals from different kindreds were found to have an identical polyalanine triplet repeat expansion ([GCG](9)) in the PABP2 gene. Individuals in this cohort had clinical and genetic characteristics of classic OPMD. Longevity was not affected, but patients experienced considerable morbidity. The origin of the PABP2 mutation in New Mexican OPMD patients is unclear, although the geographic and genetic isolation of northern New Mexicans with a long ancestry in this region may have contributed to the development of this cohort. This disease cohort represents a large and previously unrecognized health care issue in the state of New Mexico and should serve to raise the awareness of this disorder among clinicians who treat Hispanics in the Southwest and throughout the United States.

MALIGNANT APPEARING CACHEXIA IN AN OLDER PATIENT WITH BRUNS‐GARLAND SYNDROME

A 75-year-old man presented to us with a 6-month weight loss of 85 lbs. He was unable to get out of a chair and was brought in in a wheelchair by his wife. His past medical history was significant for Type II diabetes mellitus, diagnosed 20 years ago, and he hadn't seen a physician for the past 10 years. He reported that he had not taken his diabetic medications for the past 5 years and was controlling his diabetes by diet. His wife reported that for the past 6 months he had experienced progressive weight loss even though he continued to eat normally. He has also developed muscle wasting of his lower extremities and was unable to climb stairs or get out of a chair without assistance. On physical examination, the patient was found to be cachectic, with severe symmetrical muscle wasting and motor deficit of the proximal leg muscles. There was no apparent sensory impairment of the lower extremities. On laboratory evaluation the patient had a normal complete blood count, electrolytes, liver enzymes, and sedimentation rate. He had an elevated hemoglobin A1c and fasting blood glucose. The patient was initiated on a regiment of insulin and a sulfonurea, with subsequent good control of his glucose. The patient continued to loose weight, however, and had now developed diffuse deep aching pain in both thighs. An evaluation for a possible occult malignancy was initiated, with full body CT, prostate specific antigen, colonoscopy, and endoscopy results unremarkable. The patient was then sent for evaluation by endocrinology and infectious diseases; both recommended continued evaluation for occult malignancies with negative tests for HIV, tuberculosis, adrenal insufficiency, and thyroid disease. Nerve conduction studies done by neurology showed a predominant proximal lower limb axonopathy. MRI of the lumbar spine was unremarkable. Muscle biopsy was not done. The patient was treated with gabapentin 300 mg TID resulting in slow improvement of his pain syndrome. With continued diabetic control, the patient slowly gained back 65 lbs. over 10 months, with partial improvement of the proximal lower limb muscle weakness and wasting. Diabetic Amyotrophy (Bruns-Garland syndrome) is characterized by weakness followed by wasting of pelvifemoral muscles, either bilaterally or unilaterally, with associated pain.1 The pathogenesis is unknown, but it is theorized to be either metabolic or ischemic in nature. It is prevalent in .08% of diabetic patients (1.1% of type II diabetics, and .03% of type I diabetics).2 It typically affects men with type II diabetes in their fifth or sixth decade and is associated with a 10- to 30-lb. weight loss.2,3 The syndrome usually improves with glycemic control. This particular patient was much older than the typical patients, and his weight loss was much more pronounced. This unusual manifestation of diabetes must be taken into consideration when geriatric patients present with a history of type II diabetes in conjunction with weight loss and proximal limb muscle wasting and motor deficit. We as clinicians should strive to detect and characterize this syndrome further in geriatric patients, thus avoiding unnecessary, prolonged, and costly work-ups for these patients.

A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3

Autosomal recessive limb-girdle muscular dystrophies represent a genetically heterogeneous group of diseases characterized by a progressive involvement of skeletal muscles. They show a wide spectrum of clinical courses, varying from very mild to severe. Eight loci responsible for autosomal recessive limb-girdle muscular dystrophies have been mapped and six defective genes identified. In this study, we report the clinical data, muscle biopsy findings and results of genetic linkage analysis in a large consanguineous Tunisian family with 13 individuals suffering from autosomal recessive limb-girdle muscular dystrophy. Clinical features include variable age of onset, proximal limb muscle weakness and wasting predominantly affecting the pelvic girdle, and variable course between siblings. CK rate was usually high in younger patients. Muscle biopsy showed dystrophic changes with normal expression of dystrophin and various proteins of the dystrophin-associated protein complex (sarcoglycan sub-units, dystroglycan, and sarcospan). Genetic linkage analysis excluded the known limb-girdle muscular dystrophies loci as well as ten additional candidate genes. A maximum LOD score of 4.36 at &theta;=0.00 was obtained with marker D19S606, mapping this new form of autosomal recessive limb-girdle muscular dystrophy to chromosome 19q13.3.

Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations.

BACKGROUND: The autosomal recessive limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscle diseases characterised by progressive proximal limb muscle weakness. Six different loci have been mapped and...

Polymyositis associated with primary biliary cirrhosis

The coexistence of polymyositis (PM) and primary biliary cirrhosis (PBC) is rare; only nine cases have been described in English literature. We report a case of a 46-year-old woman presenting with these two autoimmune diseases. The diagnosis of PM was based on the symmetrical, proximal limb muscle weakness, elevated muscle enzymes and was confirmed with the electromyography and muscle biopsy. The diagnosis of PBC was based on the increased serum levels of alkaline phosphatase, gamma glutamyltransferase, IgM immunoglobulin, the presence of antimitochondrial antibodies and diagnostic liver biopsy.

Dermatomyositis treated with high-dose intravenous immunoglobulins and associated with panniculitis

Polymyositis and dermatomyositis are idiopathic inflammatory myopathies characterized by subacute symmetrical weakness of proximal limb and trunk muscles. Dermatomyositis is distinguished from polymyositis by the presence of rash. We describe an adult patient with treatment-resistant childhood-type dermatomyositis who made a good response to high dose intravenous immunoglobulins. Additionally, there was evidence of panniculitis which is an unusual histopathological finding in dermatomyositis.

Steroid-induced myopathy and its significance to respiratory disease: a known disease rediscovered

Skeletal muscle myopathy is a well-known side-effect of systemically administered corticosteroids. In recent years renewed attention is being paid to the involvement of the respiratory muscles and its consequent significance in pulmonary patients. Two different clinical patterns of steroid-induced muscular changes are known. In acute myopathy and atrophy after short term treatment with high doses of steroids, generalized muscle atrophy and rhabdomyolysis occur, including the respiratory muscles. Chronic steroid myopathy, occurring after prolonged treatment with moderate doses, is characterized by the gradual onset of proximal limb muscle weakness and may be accompanied by reduced respiratory muscle force. Animal studies demonstrated diaphragmatic myopathy and atrophy similar to the alterations in peripheral skeletal muscles. Fluorinated steroids induced selective type IIb (fast-twitch glycolytic) fibre atrophy, resulting in changes in contractile properties of the diaphragm. Non-fluorinated steroids may also induce histological, biochemical and functional alterations in the diaphragm. Observations in patients with collagen vascular disorders and with asthma and chronic obstructive pulmonary disease (COPD) underline the potential hazards of treatment with corticosteroids to respiratory muscle structure and function.

Peripheral nerve and vasculature involvement in myophosphorylase deficiency (mcardle’s disease)

A 60 year old white male presented with atypical chest pain and exercise-induced myalgia. Physical examination revealed slight proximal limb muscle weakness and wasting. Serum creatine phosphokinase levels were persistently elevated and electromyography showed changes consistent with a mild myopathy. Light microscopic and ultrastructural study revealed excess free glycogen within skeletal muscle, and histochemical staining showed absence of myophosphorylase activity. Biochemical quantitation confirmed the diagnosis of McArdle's disease by demonstrating absent phosphorylase activity in skeletal muscle with increased glycogen. In addition, increased amounts of free and membrane-bound glycogen were found within axons, Schwann cells, fibroblasts and occasional vascular smooth muscle and endothelial cells that had been included within the skeletal muscle biopsy. This case demonstrates more widespread glycogen accumulation than has been previously reported in McArdle's disease.