Exercise induced muscle weakness in a young adult: McArdle's disease unusual presentation.

McArdle's disease (Glycogen storage disease type V) is a rare inherited autosomal recessive disease involving defect in enzyme, glycogen phosphorylase (PYGM) which results in accumulation of glycogen mainly affecting skeletal muscles. It commonly presents in childhood and rarely in adults with symptoms like exercise intolerance, muscle weakness, cramps and fatigue. Herein, we report an unusual case of a 22 years old male in Pakistan with probable McArdle's Disease presenting with repeated episodes of generalized cramping muscle pain, exercise intolerance and haematuria. The diagnostic approach to identifying this disease as well as the differentials of other rare types of skeletal muscle disorders that should be kept in mind while dealing with a similar clinical picture, irrespective of the age of presentation, have been discussed.

[Diagnostic approach to rhabdomyolysis]. / Vignette diagnostique de l'étudiant. Approche diagnostique de la rhabdomyolyse.

Rhabdomyolysis is a clinical syndrome related to the damage of skeletal muscle. The symptomatology is often poor, but it classically includes muscle weakness, myalgia and red-brown urine. The causes may be multiple but are most frequently traumatic : the so-called "crush syndrome". The diagnosis is based on the increase in serum creatine kinase, which is sometimes associated with myoglobinuria. Rhabdomyolysis may cause severe complications, such as ionic disorders or acute kidney injury which can lead to the death of the patient.

La rhabdomyolyse est un syndrome clinique lié à la destruction du muscle squelettique. La symptomatologie est souvent pauvre et associe classiquement une faiblesse musculaire, des myalgies et des urines noirâtres. Les causes peuvent être multiples, mais sont le plus fréquemment traumatiques et regroupées sous le terme anglophone de «crush syndrome¼. Le diagnostic repose sur la majoration sérique de la créatine kinase, à laquelle s'associe parfois une myoglobinurie. Rarement bénigne, la rhabdomyolyse peut engendrer des complications sévères, telles que des troubles ioniques ou une insuffisance rénale pouvant mener au décès du patient.

Discolored Urine in Horses and Foals.

This article describes the most common causes of urine discoloration. The review includes a description of the most common disorders causing hematuria, highlighting clinical presentation, treatments, and pathophysiology. Causes of hemoglobinuria and myoglobinuria together with their mechanisms of renal injury are also reviewed.

Acute kidney injury in pediatric non-traumatic rhabdomyolysis.

BACKGROUND: Our study aimed to determine the prevalence of acute kidney injury (AKI) in pediatric non-traumatic rhabdomyolysis, and to identify factors associated with its development. METHODS: Clinical information and laboratory tests of children with rhabdomyolysis who were admitted between 2009 and 2018 were reviewed retrospectively. Rhabdomyolysis was defined by a peak serum creatine kinase (CK) level > 1000 IU/L within the first 72 h of admission. The primary outcome was the occurrence of AKI within the first 7 days of admission, which was determined by the KDIGO criteria. RESULTS: A total of 54 patients with a median age of 7.8 years old were included. Ten (18.5%) patients developed AKI. AKI was relatively rare in children with viral myositis (2.6%), whereas all patients with rhabdomyolysis related to seizure or irritability/dystonia developed AKI. Patients with AKI had higher white cell count (10.6 vs. 4.5 × 109/L) and lower serum bicarbonate (19.4 vs. 25.5 mmol/L) on admission, with higher peak serum CK (23,086.0 vs. 3959.5 IU/L). The AKI group was more likely to present with positive urine results (myoglobinuria, dipstick heme or protein ≥ 2+). Peak serum CK had a good discriminatory power for stage 2-3 AKI (AUC 0.930, p = 0.005), with an optimal cut-off of 15,000 IU/L identified from the ROC analysis. CONCLUSIONS: The overall prevalence of AKI in pediatric non-traumatic rhabdomyolysis was 18.5%. Positive urine tests (myoglobinuria, dipstick heme or protein ≥ 2+), high white cell count, lower serum bicarbonate on admission, and high peak serum CK were associated with development of AKI.

Red-Colored Urine in the Cardiac Surgical Patient-Diagnosis, Causes, and Management.

Red-colored urine occurring in the intraoperative and early postoperative periods after cardiac surgery is often a cause for concern. This observation may be a result of hematuria from pathology within the urinary tract, anticoagulant-related nephropathy, drug-induced acute interstitial nephropathy, excretion of heme pigment-containing proteins, such as myoglobin and hemoglobin, and hemolysis occurring during extracorporeal circulation. Within the kidneys, heme-containing compounds result in pigment nephropathy, which is a significant contributory factor to cardiac surgery-associated acute kidney injury. Concerted efforts to reduce red blood cell damage during cardiopulmonary bypass, together with early recognition of the at-risk patient and the institution of prompt therapeutic intervention, may improve outcomes. This review addresses the diagnosis, causes, and management of red-discolored urine occurring during and after cardiac surgery.

, , RHABDOMYOLYSIS - INDUCED ACUTE KIDNEY INJURY - AN UNDERESTIMATED PROBLEM.

Rhabdomyolysis is a condition characterized by muscle damage and the release of intracellular muscle contents into the circulation. It leads to a lot of complications e.g. hyperkalemia, hyperphosphatemia, and calcium disorders. The etiology is multifactorial. Severity ranges from mildly muscle weakness without any systemic complications, to life-threatening multi-organ damage. The most common and serious systemic complication is acute kidney injury (AKI). In the review, we address the epidemiology, causes, and treatment. The ideal would be to predict and prevent rhabdomyolysis at all, but when it is impossible, the key to successful treatment is its rapid implementation. Therapy should be selected individually, adapting to the triggers, and closely monitoring the patient's condition. Early implementation of fluid therapy appears to be crucial. Electrolyte disturbances should always be detected in the early stages and carefully treated. The use of bicarbonates or diuretics may also be helpful, but especially in the latter case, the indications should be well evaluated, remembering to avoid hypovolemia. Renal replacement therapy is often implemented due to water-electrolyte or acid-base disorders. Proper diagnosis and early therapy implementation improve patient outcomes, in particular in the face of new infectious dangers and global underestimating of the disease.

TREATMENT OF SUSPECTED EXERTIONAL MYOPATHY USING DANTROLENE IN A COYOTE ( CANIS LATRANS).

A 3-yr-old spayed female coyote ( Canis latrans) developed clinical signs of exertional myopathy after fighting with a conspecific. A diagnosis of exertional myopathy was made based on physical examination findings, probable myoglobinuria, and elevations in serum creatinine kinase activity, alanine aminotransferase activity, and potassium concentration. Dantrolene, a hydantoin analog, as well as supportive and symptomatic therapies, was used to successfully treat exertional myopathy. This is the first reported use of dantrolene in wildlife or zoo animals.

Single amino acid loss in the dystrophin protein associated with a mild clinical phenotype.

INTRODUCTION: The dystrophinopathies include a spectrum of muscle diseases caused by mutations in the dystrophin (DMD) gene. The clinical phenotype ranges from severe Duchenne muscular dystrophy to a mild phenotype with elevated creatine kinase (CK). METHODS: Clinical and molecular assessment of 7 patients carrying a single amino acid loss in the dystrophin protein (p.His1690del) caused by a c.5068_5070delCAC tri-nucleotide deletion in exon 36 of the DMD gene. RESULTS: All patients were asymptomatic or oligosymptomatic and had elevated CK levels. Febrile illness, but not exercise, induced muscle symptoms in some patients. None had evidence of cardiomyopathy. Analysis of the short tandem repeat (STR)45 locus and sequencing of exon 36 of the DMD gene indicates that c.5068_5070delCAC is a founder mutation. CONCLUSIONS: The c.5068_5070delCAC locus in the DMD gene is associated with a very mild phenotype. Further study is needed to evaluate disease progression in these patients. Muscle Nerve 55: 46-50, 2017.

Muscle Carnitine Palmitoyltransferase II Deficiency: A Review of Enzymatic Controversy and Clinical Features.

CPT (carnitine palmitoyltransferase) II muscle deficiency is the most common form of muscle fatty acid metabolism disorders. In contrast to carnitine deficiency, it is clinically characterized by attacks of myalgia and rhabdomyolysis without persistent muscle weakness and lipid accumulation in muscle fibers. The biochemical consequences of the disease-causing mutations are still discussed controversially. CPT activity in muscles of patients with CPT II deficiency ranged from not detectable to reduced to normal. Based on the observation that in patients, total CPT is completely inhibited by malony-CoA, a deficiency of malonyl-CoA-insensitive CPT II has been suggested. In contrast, it has also been shown that in muscle CPT II deficiency, CPT II protein is present in normal concentrations with normal enzymatic activity. However, CPT II in patients is abnormally sensitive to inhibition by malonyl-CoA, Triton X-100 and fatty acid metabolites. A recent study on human recombinant CPT II enzymes (His6-N-hCPT2 and His6-N-hCPT2/S113L) revealed that the wild-type and the S113L variants showed the same enzymatic activity. However, the mutated enzyme showed an abnormal thermal destabilization at 40 and 45 °C and an abnormal sensitivity to inhibition by malony-CoA. The thermolability of the mutant enzyme might explain why symptoms in muscle CPT II deficiency mainly occur during prolonged exercise, infections and exposure to cold. In addition, the abnormally regulated enzyme might be mostly inhibited when the fatty acid metabolism is stressed.

Primary Myoglobinuria: Differentiate Myoglobinuria from Hemoglobinuria.

Myoglobin is dark red colour heme containing protein, stored in muscle. Change in permeability of myolemma causes myoglobin leak in plasma, which is cleared by kidney swiftly. Differentiating myoglobinuria from hemoglobinuria is important. Clinicians concern over myoglobinuria is to protect the patient from acute renal disease. We present a case of primary myoglobinuria, its clinical symptoms, diagnosis and treatment.

Young girl presenting with exercise-induced myoglobinuria.

INTRODUCTION: The sarcoglycanopathies are a heterogeneous group of autosomal recessive limb-girdle muscular dystrophies that cause varying degrees of progressive proximal muscle weakness. METHODS: We describe the case of a Caucasian girl who presented with exercise intolerance, myalgia, and dark urine. Onset of symptoms was at age 4, and she had myalgia with physical activity throughout childhood. Creatine kinase levels were as high as 18,000. RESULTS: Immunostaining of a muscle biopsy showed mildly diminished alpha sarcoglycan staining, and SGCA gene sequencing revealed n.C229T; p.Arg77Cys (R77C) and n.C850T; p.Arg284Cys (R284C), which is associated with alpha sarcoglycanopathy. CONCLUSIONS: This patient presented with exercise intolerance, myoglobinuria, and almost normal muscle strength into adolescence, which is uncommon in sarcoglycanopathies. This uncommon presentation should be kept in mind, so that early recognition and intervention may prevent future comorbidities and help preserve the quality of life. Muscle Nerve 54: 161-164, 2016.

Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice.

BACKGROUND: Rhabdomyolysis is a clinical syndrome that comprises destruction of skeletal muscle with outflow of intracellular muscle content into the bloodstream. There is a great heterogeneity in the literature regarding definition, epidemiology, and treatment. The aim of this systematic literature review was to summarize the current state of knowledge regarding the epidemiologic data, definition, and management of rhabdomyolysis. METHODS: A systematic search was conducted using the keywords "rhabdomyolysis" and "crush syndrome" covering all articles from January 2006 to December 2015 in three databases (MEDLINE, SCOPUS, and ScienceDirect). The search was divided into two steps: first, all articles that included data regarding definition, pathophysiology, and diagnosis were identified, excluding only case reports; then articles of original research with humans that reported epidemiological data (e.g., risk factors, common etiologies, and mortality) or treatment of rhabdomyolysis were identified. Information was summarized and organized based on these topics. RESULTS: The search generated 5632 articles. After screening titles and abstracts, 164 articles were retrieved and read: 56 articles met the final inclusion criteria; 23 were reviews (narrative or systematic); 16 were original articles containing epidemiological data; and six contained treatment specifications for patients with rhabdomyolysis. CONCLUSION: Most studies defined rhabdomyolysis based on creatine kinase values five times above the upper limit of normal. Etiologies differ among the adult and pediatric populations and no randomized controlled trials have been done to compare intravenous fluid therapy alone versus intravenous fluid therapy with bicarbonate and/or mannitol.

Exercise training in metabolic myopathies.

Metabolic myopathies encompass muscle glycogenoses (GSD) and disorders of muscle fat oxidation (FAOD). FAODs and GSDs can be divided into two main clinical phenotypes; those with static symptoms related to fixed muscle weakness and atrophy, and those with dynamic, exercise-related symptoms that are brought about by a deficient supply of ATP. Together with mitochondrial myopathies, metabolic myopathies are unique among muscle diseases, as the limitation in exercise performance is not solely caused by structural damage of muscle, but also or exclusively related to energy deficiency. ATP consumption can increase 50-100-fold in contracting, healthy muscle from rest to exercise, and testing patients with exercise is therefore an appropriate approach to disclose limitations in work capacity and endurance in metabolic myopathies. Muscles rely almost exclusively on muscle glycogen in the initial stages of exercise and at high work intensities. Thus, patients with GSDs typically have symptoms early in exercise, have low peak work capacities and develop painful contractures in exercised muscles. Muscle relies on fat oxidation at rest and to a great extent during prolonged exercise, and therefore, patients with FAODs typically develop symptoms later in exercise than patients with GSDs. Due to the exercise-related symptoms in metabolic myopathies, patients generally have been advised to shun physical training. However, immobility is associated with multiple health issues, and may even cause unwanted metabolic adaptations, such as increased dependence on glycogen use and a reduced capacity for fatty acid oxidation, which is detrimental in GSDs. Training has not been studied systematically in any FAODs and in just a few GSDs. However, studies on single bouts of exercise in most metabolic myopathies show that particularly moderate intensity aerobic exercise is well tolerated in these conditions. Even low-intensity resistance training of short duration is tolerated in McArdle disease. Training in patients with FAOD potentially can also expand the metabolic bottleneck by increasing expression of the defective, but partially functional enzyme. Exercise performance in metabolic myopathies can be improved by different fuel supplementations and dietary interventions and should be considered as adjunct therapy to exercise training.

[Brown urine : Myoglobin-induced renal failure after concomitant administration of simvastatin and amiodarone]. / Brauner Urin : Myoglobininduziertes Nierenversagen nach gleichzeitiger Gabe von Simvastatin und Amiodaron.

Rhabdomyolysis is a rare but well-known complication of statin therapy. The risk is considerably increased when concomitant drugs are administered that inhibit metabolism and breakdown via the cytochrome CYP3A4. We report a case of myoglobin-induced acute renal failure secondary to the concomitant use of simvastatin and amiodarone. The risk of rhabdomyolysis is mainly determined by the statin dose; in the case of the concomitant use of CYP3A4 inhibitors, a maximal daily dose of 20 mg is recommended to avoid harmful drug interactions.

McArdle's Disease: A Differential Diagnosis of Metabolic Myopathies.

McArdle's disease, also known as glycogen storage disease type V or McArdle syndrome, is a pure muscle myopathy with an autosomal recessive inheritance pattern. It is caused by mutations in the gene that encodes muscle phosphorylase. Symptoms typically begin in late adolescence or early adulthood, presenting as exercise intolerance. This review focuses on the diagnosis of McArdle's disease, initially manifesting as a clinical picture of rhabdomyolysis in an 18-year-old male patient with a history of minor thalassemia who had been followed in pediatric consultation since age three for failure to thrive. After excluding common causes such as alcohol consumption, drug use, traumatic muscle compression, and other conditions, the diagnosis of McArdle's disease was considered. The diagnosis was supported by laboratory tests showing myoglobinuria and elevated creatine kinase levels, as well as the absence of increased serum lactate following ischemic exercise. Genetic testing confirmed the presence of mutations in the PYGM gene, corroborating the diagnosis. Treatment includes administering a diet rich in slow-absorbing carbohydrates, regular low-intensity physical exercise, and, in some cases, supplementation with vitamin B6 and creatine. The prognosis is generally favorable with proper disease management, although vigorous exercise should be avoided to prevent complications such as severe muscle injury and rhabdomyolysis. Although McArdle's disease is a rare condition, it is likely underdiagnosed. Ideally, it should be considered in the differential diagnosis of rhabdomyolysis in all patients with symptoms of exercise intolerance and/or recurrent myoglobinuria.

Profound Rhabdomyolysis and Viral Myositis Due to SARS-CoV-2: A Case Report.

The novel SARS-CoV-2 introduced several new inflammatory conditions including SARS-CoV-2-associated rhabdomyolysis and viral myositis. We present a 22-year-old man who noted a week of cough followed by myalgias, dark-colored urine, and decreased oral intake. He was found to have acute nontraumatic rhabdomyolysis after an acutely positive SARS-CoV-2 test. Initial creatine kinase (CK) level was above the reference range as were liver enzymes reflective of muscle breakdown. Treatment involved fluid resuscitation and pain control, with close monitoring of kidney, liver, and skeletal markers over five days of hospitalization till there was clinical and symptomatic improvement.

Unraveling Complexities: Rhabdomyolysis, Acute Renal Injury, and Compartment Syndrome Following a Wasp's Sting.

This study delves into the rare occurrence of rhabdomyolysis induced by wasp stings, emphasizing its toxic systemic repercussions. Drawing parallels with documented instances of insect bites worldwide, including those by honey bees and Africanized bees, the research explores the correlation between multiple wasp stings and acute renal failure associated with rhabdomyolysis. The venom's active components, such as amines, kinins, and histamine-releasing peptides, underpin toxic systemic reactions, leading to hemolysis, coagulopathy, and severe cytotoxicity-induced acute renal failure. Noteworthy is the emergence of blackish necroses at the sting site, suggesting intense cytotoxicity. The study also highlights skin necrosis as a prognostic indicator for toxic systemic reactions. The presented case manifests an anaphylaxis-like reaction, revealing insights into toxic responses devoid of IgE-mediated allergic reactions. Timely intervention, encompassing hydration, transfusion, and dialytic support, proves imperative in scenarios involving multiple wasp stings, offering successful outcomes documented through plasma exchange in severe cases. This research prompts considerations beyond anaphylaxis, urging exploration of severe toxic systemic reactions in the context of multiple wasp stings.

Clinical Diagnosis of Rhabdomyolysis without Myoglobinuria or Electromyographic Abnormalities in a Dog.

A 2-year-old female neutered Old German Shepherd was presented for acute non-ambulatory tetraparesis. Upon presentation to the emergency department, hematology and biochemical blood tests revealed no abnormalities aside from mildly elevated C-reactive protein levels (22.5 mg/L, reference range 0.0-10.0) and immeasurable creatine kinase (CK) activity. Neurological evaluation the next day revealed ambulatory tetraparesis, general proprioceptive deficits, mild ataxia and dubious diffuse myalgia. Withdrawal reflexes were weak on both thoracic and pelvic limbs. The CK was determined to be significantly elevated at that point (32.856 U/L, ref. range 10.0-200.0). Urinalysis revealed no abnormalities. An electromyographic (EMG) study of thoracic limb, paraspinal and pelvic limb muscles revealed no abnormalities. A magnetic resonance imaging (MRI) study of the cervicothoracic spinal cord was performed and revealed no abnormalities. A presumptive clinical diagnosis of rhabdomyolysis without myoglobinuria or EMG abnormalities was formed. Muscular biopsies were declined due to the rapid clinical improvement of the dog. A follow-up showed the progressive decline of CK activity to normal values and clinical remission of signs. A diagnosis of rhabdomyolysis was concluded based on clinical signs, consistent CK activity elevations and the response to supportive treatment for rhabdomyolysis, despite the absence of myoglobinuria and EMG abnormalities. Rhabdomyolysis should not be excluded based on the lack of EMG abnormalities or myoglobinuria in dogs.

Fatal rhabdomyolysis caused by COVID-19 infection: a case report.

COVID-19 is a systemic viral disease complicated with medical conditions. Severe rhabdomyolysis during the COVID-19 course is not until now well known. Case presentation: The authors presented a 48-year-old female with fatal rhabdomyolysis caused by COVID-19 infection. She was referred to us with cough, generalized myalgia and arthralgia, and fever during the last week. Laboratory results showed an elevated erythrocyte sedimentation rate, elevated C-reactive protein level, and elevated creatine kinase. The nasopharyngeal swab confirmed the diagnosis of coronavirus 2 RNA infection. She was managed initially in the COVID-19 isolation department. Three days later, she was transferred to the intensive care unit and mechanically ventilated. Laboratory results were consistent with rhabdomyolysis. She died because of cardiac arrest due to continuous hemodynamic deterioration. Clinical discussion: Rhabdomyolysis is a serious condition that can be fatal or cause disability. Rhabdomyolysis cases have been reported in COVID-19 patients. Conclusion: Rhabdomyolysis cases have been reported in COV19 patients. Further studies are needed to understand the mechanism and to optimize the treatment.

Rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog.

OBJECTIVE: To report a case of rhabdomyolysis and myoglobinuria following single induction dose of propofol in a dog. CASE SUMMARY: A 5-year-old intact male Shih-Tzu dog was presented for pigmenturia occurring a few hours following anesthesia for comprehensive oral health assessment and treatment. After premedication with IV diazepam (0.5 mg/kg), anesthesia was induced with IV propofol (4 mg/kg) and maintained with isoflurane vaporized in oxygen. A few hours following recovery from anesthesia, the dog developed rhabdomyolysis and myoglobinuria associated with increased serum alanine aminotransferase and C-reactive protein concentrations, as well as mild hypokalemia and euglycemic glycosuria. Approximately 48 hours after IV fluid therapy, the dog was clinically normal, and myoglobinuria progressively resolved. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case description of rhabdomyolysis and myoglobinuria following a single dose of injectable propofol.