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Looking at the urine for diagnostic purposes, once performed by ancient Egyptians, can still provide some valuable clues in modern medicine. Several diseases have been named after their associated urine color and this underlines the clinical value of visual urine inspection: blue diaper disease, purple urine bag syndrome, black urine disease or porphyria. Abnormal urine color could be challenging for the clinician: it may reveal neoplastic disease (urologic cancer; melanoma), cell lysis (rhabdomyolysis; hemolysis), infection (lymphatic filariasis; malaria), enzyme deficiency (porphyria; alkaptonuria), medication or food intake. In this article, we present the diagnostic approach, the mechanisms involved and the main causes of abnormal urine color.

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.

This retrospective study evaluated the phenotypic and genotypic features of 14 patients with McArdle disease attending the West of Scotland adult muscle clinic. Although all patients experienced exercise-induced cramps, exercise intolerance and hyperCKaemia, only 71% (n = 10) experienced the second wind phenomenon, rhabdomyolysis and/or myoglobinuria. We observed a high rate of fixed muscle weakness (50%; n = 7), coronary artery disease (36%; n = 5), and psychological comorbidity (50%; n = 7). Although 79% had symptom onset in the first decade of life, the mean age at presentation and at genetic diagnosis was 43.8 years and 47.7 years, respectively. 93% had at least one copy of the common PYGM pathogenic variant, c.148C > T, p.(Arg50*), with 50% (n = 7) of the cohort being homozygous. Our cohort highlights the phenotypic variability seen in McArdle disease and underscores the potential for late-onset presentations. It emphasises the need for improved awareness and recognition of this condition amongst neurologists, rheumatologists and general physicians. A history of exercise intolerance and second wind phenomenon may not always be volunteered by the patient, underscoring the need to ask specific questions in clinic to extrapolate the relevant symptoms in this patient cohort.

A 60-year-old Japanese woman presented with subacute progressive muscle pain and weakness in her proximal extremities. She was diagnosed with influenza A (H3N2) infection a week before the onset of muscle pain. At the time of admission, she exhibited weakness in the proximal muscles of the upper and lower limbs, elevated serum liver enzymes and creatinine kinase, and myoglobinuria. She did not manifest renal failure and cardiac abnormalities, indicating myocarditis.Electromyography revealed myogenic changes, and magnetic resonance imaging of the upper limb showed abnormal signal intensities in the muscles, suggestive of myopathy. Muscle biopsy of the biceps revealed numerous necrotic regeneration fibers and mild inflammatory cell infiltration, suggesting immune-mediated necrotizing myopathy (IMNM). Necrotized muscle cells were positive for human influenza A (H3N2). Autoantibody analysis showed the presence of antibodies against the signal recognition particle (SRP), and the patient was diagnosed with anti-SRP-associated IMNM. She was resistant to intravenous methylprednisolone pulse therapy but recovered after administration of oral systemic corticosteroids and immunoglobulins. We speculate that the influenza A (H3N2)infection might have triggered her IMNM. Thus, IMNM should be considered as a differential diagnosis in patients with proximal muscle weakness that persists after viral infections., International Journal of Infectious Diseases, 103, pp.33-36: 2020

Introduction McArdle´s disease or glycogenosis type V is a rare disease due to deficiency of muscle myophosphorylase leading to inability to degrade glycogen at this level. Patients have fatigue, pain, and cramps on a regular basis. In addition, after intense exercise or stressful situation, they are exposed to cellular lysis. This can occur in the form of rhabdomyolysis and myoglobinuria, a potentially serious clinical syndrome if not treated quickly. Case evaluation We present the care plan of a 38-year-old man with McArdle´s disease and secondary rhabdomyolysis on physical exercise, which required attention in the Emergency Department for 24 h, as well as his subsequent admission to the ward. A nursing evaluation was performed following the care model of Virginia Henderson. Diagnosis Priority was given to nurse diagnoses: (00016) deterioration of urinary elimination, (00092) activity intolerance, (00093) fatigue and (00132) acute pain; and potential complication: risk of acute renal failure. Planning The Care Plan is developed following the NANDA-NIC-NOC methodology, with special attention to alterations in the elimination and musculoskeletal system. The diuresis is monitored. Fluid replenishment is performed, and analgesic medication is given. Discussion There is little literature on the nursing care of patients with McArdle’s disease, which has limited the comparison of our results with those of other authors. However, given the good response of the subject through fluid replacement, optimal pain control, rest, they made a rapid recovery.

McArdle's disease (glycogen storage disease type V) is an energy-dependent disorder of skeletal muscle caused by a deficiency of myophosphorylase, an important enzyme of carbohydrate metabolism that converts glycogen to glucose-1-phosphate. A 46 year-old man was sent to the rheumatology outpatient department with a 3-year history of severe exercise-induced cramps and myalgias. The episodes began when he worked in France and used to practice ski and snowboard in the Alps Mountain, with exercise intolerance, muscle cramps, and myoglobinuria. The laboratory results showed elevated serum creatine kinase levels (∼15,000 U/L), and the biopsy of the deltoid muscle revealed glycogen subsarcolemmal vacuoles and absence of myophosphorylase enzymatic activity. This clinical case emphasises the importance of taking into account this metabolic disorder when faced with a patient with exercise intolerance and cramps, especially after vigorous/anaerobic exercise and elevated levels of CK activity. It is fundamental to explain the aetiology of the patient symptoms in order to improve quality of life and avoid unnecessary complications.

McArdle disease or type V glycogenosis is a rare metabolic myopathy consisting of muscle loss and weakness. These patients have risks associated with anaesthesia. They can present with hypoglycaemia, rhabdomyolysis, acute renal failure, and electrolyte changes. It has also been associated with a higher incidence of malignant hyperthermia during the anaesthetic procedure. Intermittent compression due to the measurement of non-invasive pressure, postures on the operating table that may cause muscle contractures, or tremor caused by hypothermia or anaesthesia itself, may trigger rhabdomyolysis in these patients. In this article we present our experience in submitting a patient with McArdle's syndrome to general anaesthesia for total thyroidectomy due to multinodular euthyroid goitre.

Idiopathic toe walking (ITW) is a pathological gait pattern in which children walk on their tip toes with no orthopedic or neurological reason. Physiological characteristics of the gastrocnemius muscles, the Achilles tendon, and the foot of toe walkers differ from subjects with a plantigrade walking pattern. McArdle’s disease is characterized by the inability to break down muscle glycogen. It is an autosomal-recessive condition, characterized by low exercise tolerance, muscular atrophy at the shoulder girdle, episodes of myoglobinuria after vigorous physical activities and the occurrence of the second wind phenomenon. The aim of this review is to present the case studies of two subjects who were originally diagnosed as idiopathic toe walkers, but were then found to have McArdle’s disease. This review will describe some physical characteristics that distinguish McArdle´s disease from Idiopathic toe walkers.

Detainees may be subjected to torture and extra-judicial execution by State actors and terrorists. But, the pathology of torture has not been well-described. This is due to the lack of autopsies performed on victims of torture, mostly due to the disposal of the bodies of the victims by their torturers. On this basis, the cause of death of detainees subjected to torture is often a matter of speculation or remains obscure. This paper provides an overview of the pathology of torture based on the authour's experience with the autopsies of torture victims. At autopsy, many different types of inflicted injuries may be observed, often ranging in severity. However, three recurrent patterns of trauma that are the hallmarks of torture were recognized by the authour: (1) blunt impact trauma characterized by bruises, patterned injuries, and internal injuries; (2) electrical and thermal injuries; and (3) injuries from stress positions that occur from prolonged suspension. The most under-recognized form of fatal torture are the complications of stress positions related to suspension of the victim's body by the upper, or lower extremities. For example, prolonged suspension by reverse hanging (suspension of the victim's body by the wrists or forearms with the arms extended backward at the shoulder joint) can cause over-stretching and necrosis of the muscles of the shoulder, resulting in fatal myoglobinuric renal failure. It is essential that autopsies be performed on all detainees who die in custody, to determine if torture played a role in death. Furthermore, the true nature of the injuries sustained often remains obscure unless a musculocutaneous dissection is performed. Specifically, dissection of the back, limbs and the soles of the feet, as well as the shoulders and knees is essential to determine if specific forms of torture have been applied. This is especially true for fatal complications of stress positions. Seeking the truth about the medical consequences of fatal torture will raise awareness about torture-related injuries, assist in rehabilitation of torture survivors, and strengthen forensic humanitarian action.

Malignant hyperthermia is a hypermetabolic syndrome that appears in susceptible patients after exposure to certain anaesthetic drugs (succinylcholine, inhalation anaesthetics). Its incidence in Spain is 1 in 40,000 adults, with a 10% mortality rate. It is induced by an abnormal regulation of the ryanodine receptors, producing a massive release of calcium from the sarcoplasmic reticulum in the striate muscle. Clinical manifestations include: CO2 increase, tachycardia, haemodynamic instability, metabolic and respiratory acidosis, profuse sweating, hyperpyrexia, CPK increase, myoglobinuria, kidney failure, disseminated intravascular coagulation (DIC), and ending in cardiac arrest. Dantrolene sodium is a ryanodine receptor antagonist, and inhibits the release of intracellular calcium. Definitive diagnosis is achieved by the exposure of muscle fibres to caffeine and halothane. Protocols can help guarantee a reliable and secure management when this severe event occurs.

Pathogenic variants in the PGAM2 gene are associated with glycogen storage disease type X (GSDX) and is characterized by exercise induced muscle cramping, weakness, myoglobinuria, and often tubular aggregates in skeletal muscle. We report here a patient diagnosed with GSDX at 52 years of age with a normal increase in post-exercise lactate with both anaerobic and aerobic exercise. Genetic testing found two novel PGAM2 variants (c.426C > A, p.Tyr142Ter and c.533delG, p.Gly178Alafs*31).

Rhabdomyolysis with myoglobinuria is a recognized complication of dystrophinopathies. It can be triggered by infections, exercise or volatile anesthetics. To our knowledge, it has never been reported in boys with Duchenne muscular dystrophy (DMD) after the administration of bisphosphonates. We report two patients with DMD who presented an apparent transient rhabdomyolysis with myoglobinuria after zoledronate administration. Possible mechanisms could involve hypophosphatemia, a known dose-dependent side effect of bisphosphonates, and/or direct myotoxicity of biphosphonates. Physicians and families should be aware of rhabdomyolysis with myoglobinuria as a potential uncommon side effect of bisphosphonates in DMD, in particular of zoledronate.

Muscle phosphorylase kinase b deficiency (PhK) is a rare disorder of glycogen metabolism characterized by exercise-induced myalgia and cramps, myoglobinuria and progressive muscle weakness. PhK deficiency is due to mutations in the PHKA1 gene inherited in an X-linked manner and is associated to glycogenosis type VIII (GSD VIII also called GSD IXd). PHKA1 gene codes for the αM subunit of the PhK, a multimeric protein complex responsible for the control of glycogen breakdown in muscle. Until now, few patients have been reported with X-linked recessive muscle PhK deficiency due to PHKA1 mutations. All reported patients presented with exercise intolerance and mild myopathy and one of them had cognitive impairment, leading to speculate about a central nervous system involvement in GSD VIII. Here we report in a sibling a novel mutation in the PHKA1 gene associated with a progressive myopathy, exercise intolerance, muscle hypertrophy and cognitive impairment as an associated feature. This report expands the genetic and clinical spectrum of the extremely rare PHKA1-related PhK deficiency and presents new evidences about its involvement in brain development.

Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is gradually gaining recognition. In this case series, we describe the presentation of ALPE in the emergency department setting and its clinical course. In Case 1, an 18-year-old man presented with acute-onset nausea, vomiting, and right flank pain after playing basketball, with a creatinine level of 6.42 mg/dL on initial presentation. He received fluid therapy and intravenous furosemide for 2 days. His creatinine level was 1.80 mg/dL on day 8 and finally declined to 0.71 mg/dL on day 39. In Case 2, a 31-year-old man presented with acute-onset nausea and right lower abdominal pain after swimming, with a creatinine level of 4.68 mg/dL on initial presentation. He only received fluid therapy, and his creatinine level finally declined to 0.90 mg/dL on day 11. In both cases, severe loin pain began after anaerobic exercise, and acute kidney injury without myoglobinuria was observed. The findings of our case series suggest that emergency physicians should consider ALPE in the differential diagnosis of abdominal and loin pain accompanied by an elevated creatinine level in young patients because it can be treated conservatively and has a good prognosis. Moreover, watchful waiting is recommended for ALPE while also emphasizing the need to exclude potentially life threatening or treatable kidney diseases.

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.

Background Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. Objective To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. Methods We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. Results Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18years (range, 2–47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2years. Fukutin-related protein ( FKRP ) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200IU/L; range, 600–3600). Conclusion Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy.

Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles.The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

Phosphoglycerate mutase enzyme deficiency in muscle causes a metabolic myopathy (glycogen storage disease X) characterized by exertional muscle contractures, weakness, hyperCKemia, and myoglobinuria. Six different autosomal recessive variants in PGAM-M have been described thus far (Salameh et al., 2013). In this case report, we report a novel disease-causing variant. A 52-year-old African-American woman presented with exertional muscle contractures, myalgias, and weakness since childhood including an episode of rhabdomyolysis. Neurologic examination and EMG were normal. CK was mildly elevated at rest and over 20,000 U/L during her episode of rhabdomyolysis. Muscle biopsy revealed subsarcolemmal collections suggestive of tubular aggregates. Phosphoglycerate mutase activity was 8% of the reference value. PGAM-M sequencing showed compound heterozygous variants: c.233G>A, which has been found only in African-Americans with this disease, and a novel variant, c.278G>A. This case expands the genetic spectrum of phosphoglycerate mutase deficiency.

Rhabdomyolysis is a serious and potentially life threatening condition. Although consensus criteria for rhabdomyolysis is lacking, a reasonable definition is elevation of serum creatine kinase activity of at least 10 times the upper limit of normal followed by a rapid decrease of the sCK level to (near) normal values. The clinical presentation can vary widely, classical features are myalgia, weakness and pigmenturia. However, this classic triad is seen in less than 10% of patients. Acute renal failure due to acute tubular necrosis as a result of mechanical obstruction by myoglobin is the most common complication, in particular if sCK is >16.000 IU/l, which may be as high as 100,000 IU/1. Mortality rate is approximately 10% and significantly higher in patients with acute renal failure. Timely recognition of rhabdomyolysis is key for treatment. In the acute phase, treatment should be aimed at preserving renal function, resolving compartment syndrome, restoring metabolic derangements, and volume replacement. Most patients experience only one episode of rhabdomyolysis, mostly by substance abuse, medication, trauma or epileptic seizures. In case of recurrent rhabdomyolysis, a history of exercise intolerance or a positive family history for neuromuscular disorders, further investigations are needed to identify the underlying, often genetic, disorder. We propose a diagnostic algorithm for use in clinical practice. (C) 2014 Elsevier B.V. All rights reserved.

Metabolic and mitochondrial myopathies encompass a heterogeneous group of disorders that result in impaired energy production in skeletal muscle. Symptoms of premature muscle fatigue, sometimes leading to myalgia, rhabdomyolysis, and myoglobinuria, typically occur with exercise that would normally depend on the defective metabolic pathway. But in another group of these disorders, the dominant muscle symptom is weakness. This article reviews the clinical features, diagnosis, and management of these diseases with emphasis on the recent literature.

Exertional fatigue early in exercise is a clinical hallmark of muscle glycogenoses, which is often coupled with painful muscle contractures and episodes of myoglobinuria. A fundamental biochemical problem in these conditions is the impaired generation of ATP to fuel muscle contractions, which relates directly to the metabolic defect, but also to substrate-limited energy deficiency, as exemplified by the "second wind" phenomenon in McArdle disease. A number of secondary events may also play a role in inducing premature fatigue in glycogenoses, including (1) absent or blunted muscle acidosis, which may be important for maintaining muscle membrane excitability by decreasing chloride permeability, (2) loss of the osmotic effect related to lactate accumulation, which may account for absence of the normal increase in water content of exercised muscle, and thus promote higher than normal concentrations of extracellular potassium in exercising muscle and (3) exaggerated accumulation of ADP during exercise that may inhibit sodium-potassium and calcium-ATPases. Disorders of muscle glycogenolysis and glycolysis reveal the crucial role of these metabolic processes for supplying both anaerobic and aerobic energy for muscle contraction; and the pathological fatigue that occurs when glycogenolysis and/or glycolysis is blocked imply an important role for theses metabolic pathways in normal muscle fatigue.

Muscle phosphofructokinase (PFKM) deficiency, a rare disorder of glycogen metabolism also known as glycogen storage disease type VII (GSDVII), is characterized by exercise intolerance, myalgias, cramps and episodic myoglobinuria associated with compensated hemolytic anaemia and hyperuricemia. We studied five patients with PFKM deficiency coming from different Italian regions. All probands showed exercise intolerance, hyperCKemia, cramps and myoglobinuria. One patient had a mild hypertrophic cardiomyopathy. Biochemical studies revealed residual PFK activity ranging from 1 to 5%. Molecular genetic analysis identified four novel mutations in the PFKM gene. In our series of patients, clinical and laboratory features were similar in all but one patient, who had an unusual phenotype characterized by 25years disease history, high CK levels, hypertrophic cardiomyopathy with paroxysmal atrial fibrillation without fixed muscle weakness.

IntroductionFacioScapuloHumeral Muscular Dystrophy (FSHD), a disease linked to a heterozygous D4Z4 deletion on chromosome 4q35, typically starts with shoulder-girdle and facial muscle involvement. Atypical presentations have occasionally been reported, but their frequency has still not been defined.Patients and methodsWe studied the occurrence rate of FSHD with atypical onset in 122 symptomatic subjects from 76 unrelated families with genetically confirmed FSHD. These 75 males and 47 females, with a mean age of 49 years (range: 11–85), had a mean EcoRI fragment of 25kb (range: 11–38).ResultsTypical shoulder-girdle or facial weakness at onset was reported by 88 patients (72%). Unusual presentations included: foot drop in 16 (13%) and proximal lower limb weakness in eight patients (7%). Two cases at onset manifested quite atypical, apparently non-FSHD-related syndromes: a 42-year-old woman presented with infantile epilepsy and a 41-year-old man with myoglobinuria. In the latter patient, DNA analysis detected a 4q35 deletion associated to an heterozygous CAPN3 mutation.ConclusionFSHD presentation with foot drop or lower limb proximal weakness appeared to be more frequent than expected. This type of weakness at onset has to be considered premature, but still representative of disease-related muscle involvement. Quite atypical onset appears very rare and calls for further investigation on non-FSHD-related etiology.

Loss of mobility influences the quality of life for patients with neuromuscular diseases. Common measures of mobility and chronic muscle damage are the six-minute walk test and serum creatine kinase. Despite extensive pre-clinical studies of therapeutic approaches, characterization of these measures is incomplete. To address this, a six-minute ambulation assay, serum creatine kinase, and myoglobinuria were investigated for the mdx mouse, a dystrophinopathy mouse model commonly used in pre-clinical studies. mdx mice ambulated shorter distances than normal controls, a disparity accentuated after mild exercise. An asymmetric pathophysiology in mdx mice was unmasked with exercise, and peak measurements of serum creatine kinase and myoglobinuria were identified. Our data highlights the necessity to consider asymmetric pathology and timing of biomarkers when testing potential therapies for muscular dystrophy.

Mutations of PYGM, the gene encoding human myophosphorylase, produce a metabolic myopathy characterised by exercise intolerance and, in some patients, myoglobinuria. To illustrate the clinical and laboratory features of myophosphorylase deficiency, we describe 10 patients diagnosed in Auckland, New Zealand, between 1989 and 2009. We review the clinical, biochemical, and histologic features and the results of mutation analysis. All patients reported exercise intolerance since childhood or the teenage years, starting within minutes of moderate or intense exertion. The "second wind" phenomenon, or myoglobinuria, were each reported in about half the patients. The serum creatine kinase concentration was elevated in all patients where this had been measured. Muscle biopsies revealed subsarcolemmal vacuolation and histochemical absence of myophosphorylase. Analysis of PYGM showed mutations in all alleles, most commonly Arg49Ter or Gly204Ser. One patient harbored a novel mutation, Pro488Arg, predicted to seriously disrupt the tertiary structure of the enzyme. Myophosphorylase deficiency produces a fairly uniform set of symptoms, and consistent elevation of the serum creatine kinase concentration. The diagnosis can be confirmed in most patients by mutation analysis using a blood sample.

Acute kidney injury (AKI) frequently afflicts patients undergoing cardiopulmonary bypass and independently predicts death. Both hemoglobinemia and myoglobinemia are independent predictors of postoperative AKI. Release of free hemeproteins into the circulation is known to cause oxidative injury to the kidneys. This study tested the hypothesis that postoperative AKI is associated with both enhanced intraoperative hemeprotein release and increased lipid peroxidation assessed by measuring F₂-isoprostanes and isofurans. In a case-control study nested within an ongoing randomized trial of perioperative statin treatment and AKI, we compared levels of F₂-isoprostanes and isofurans with plasma levels of free hemoglobin and myoglobin in 10 cardiac surgery AKI patients to those of 10 risk-matched controls. Peak plasma free hemoglobin concentrations were significantly higher in AKI subjects (289.0 ± 37.8 versus 104.4 ± 36.5mg/dl, P = 0.01), whereas plasma myoglobin concentrations were similar between groups. The change in plasma F₂-isoprostane and isofuran levels (repeated-measures ANOVA, P = 0.02 and P = 0.001, respectively) as well as the change in urine isofuran levels (P = 0.04) was significantly greater in AKI subjects. In addition, change in peak plasma isofuran levels correlated not only with peak free plasma hemoglobin concentrations (r² = 0.39, P = 0.001) but also with peak change in serum creatinine (r² = 0.20, P = 0.01). Postoperative AKI is associated with both enhanced intraoperative hemeprotein release and enhanced lipid peroxidation. The correlations among hemoglobinemia, lipid peroxidation, and AKI indicate a potential role for hemeprotein-induced oxidative damage in the pathogenesis of postoperative AKI.

Background To explore the value of quantitative magnetic resonance imaging (i.e., T2 map technique) in the diagnosis of crush injury in rabbit hind limb muscles. Materials and Methods We established a rabbit hind limb crush injury model and performed examinations on magnetic resonance imaging (MRI) (T1WI, T2WI, and T2 map), muscle pathology, serum level of muscular troponin (sTnI), and urine myoglobin (Myo) at 1, 3, 7, 14, and 30 d after injury to investigate the correlation of MRI, library examination, and histopathology. Results T2WI of the injured muscle showed high signal intensity at 1, 3, and 7 d after crush injury and the T2 value continued to rise. The pathologic findings of the muscle included swollen and ruptured cells, expanded extra-cellular space, inflammatory reactions, and fine muscle fiber regeneration. The serum sTnI and urine Myo were high. At 14 d, these indices returned to normal gradually. The T2WI changes and T2 value were positively associated with the pathological changes of the muscles, serum sTnI and urine Myo. However, the signal intensity of T1WI did not vary significantly at different time points. Conclusion T2WI and T2 value from T2 mapping are very useful methods of choice to evaluate the distribution and extension of the affected muscles. The high signal intensity on T2WI of the affected muscles after crush injury may be due to an increased extracellular space, local inflammation, and incomplete muscle fiber regeneration.

Introduction Rhabdomyolysis, which is defined as the degradation and disintegration of striated muscle, is an acute and possibly fatal clinical syndrome. Migratory quail consumption (Coturnism) is an unusual reported cause of acute rhabdomyolysis. Acute renal failure occurring only a few hours after migratory quail ingestion is presented in our case. Case history A 58-year-old male applied to the emergency centre with weakness, muscle pain, nausea, vomiting, decreased and darkened urine that started approximately 12h prior to his admittance. While no other possible cause for rhabdomyolysis was present, migratory quail meat ingestion 4h prior to the symptoms was reported in the history. Laboratory results revealed abnormal kidney function tests and raised liver enzymes. Prominent myoglobinuria and proteinuria were observed in the urine sample. Considering the patient's history, clinical findings and laboratory abnormalities, poisoning and acute rhabdomyolysis due to consumption of quail were diagnosed. The patient was hospitalised and treated symptomatically in the following days. The treatment resulted in the complete resolution of symptoms and signs. Abnormal blood values gradually decreased to normal levels and the patient was successfully discharged. Discussion One of the important complications of rhabdomyolysis is acute renal failure. Acute renal failure following rhabdomyolysis is seen in around 10–40% of cases. Given that Coturnism is a rare cause of acute rhabdomyolysis, renal failure due to Coturnism has only been reported on a few occasions. A diet of hemlock seeds by the birds, in addition to a hereditary enzyme deficiency is suspected to be the pathological basis for the disease. In severe cases rhabdomyolysis can result in shock or acute renal failure which may necessitate dialysis. Supportive treatment with appropriate volume replacement, urinary alkalinisation and aggressive diuresis is usually sufficient and recovery occurs quickly.

Objective: To describe a case of quetipiane- and escitalopram-associated rhabdomyolysis and secondary acute renal failure in a young adult suffering from recurrent depression. Methods: detailed clinical description of the subject’s case and relevant literature was reviewed. Results: A 35-year old male suffering from recurrent mayor depression treated with quetiapine and escitalopram, developed rhabdomyolysis and acute renal failure after ingesting an overdose of quetiapine (900 mg). Quetiapine and other antipsychotics have been related with rhabdomyolysis with or without renal failure in association or not with neuroleptic malignant syndromes.

www.jpedhc.org was his first spin class, and although he tired, he kept going in order to keep up with the rest of the class. During the prior month, he had started conditioning workouts, which consisted of lifting weights, squats, and treadmill running, and he experienced no significant muscle soreness or weakness. The adolescent claimed to be well hydrated while working out and used a 100% whey protein dietary supplement after exercising. After his workout 3 days ago, he admitted drinking alcohol but denied the use of other drugs. He does not routinely take other medications or use dietary supplements, such as creatine.

Study Objective To assess whether regular statin therapy enhances muscular and hepatic deterioration and muscle complaints in patients undergoing elective arthroplasty. Design Prospective, case-controlled, observational study. Setting Tertiary-level university teaching hospital in Eastern Finland. Patients 48 ASA physical status I, II, and III patients, aged 51 to 84 years, 24 of whom were scheduled for hip arthroplasty (12 pts with and 12 without statin therapy) and 24 patients who were to undergo knee arthroplasty (12 pts with and 12 without statin therapy). Interventions Before and after surgery, all patients were interviewed for muscular and hepatic symptoms and signs. Main Measurements S-creatine kinase, S-alanine aminotransferase, P-creatinine, S-lactate dehydrogenase, P-potassium, S-myoglobin, and U-myoglobin were measured at baseline and at 6, 24, and 72 hours after surgery. Main Results S-creatine kinase and S-myoglobin increased in all study groups at 6 hours after surgery and remained elevated for 72 hours, with no differences noted in patients treated with or without statins. There was no increase in the amount of muscular or hepatic complaints after surgery. Conclusion Long-term statin therapy does not appear to increase the risk of muscular adverse effects in patients receiving major endoprosthesis surgery.

A 39-year-old woman collapsed after oral intake of 3,4-methylenedioxymethyl-amphetamine (MDMA, "ecstasy"). After ingestion of the drug, she had felt persistent discomfort in her anterior chest area, and lost consciousness for a few minutes on the following morning. She was transported to a hospital and died seven days after collapse. A serum sample obtained on admission revealed an MDMA concentration of 1.2mg/L, but no evidence of any other drug including amphetamine, methamphetamine, or other ring-substituted amphetamines. Microscopic examination at autopsy revealed striking changes in the heart, including small foci of myocyte necrosis with a surrounding macrophage inflammatory response, foci of fibrosis, and calcification accompanied by myocyte necrosis, these changes being predominant in the right ventricle. In the liver, hepatic necrosis was observed with fatty degeneration accompanied by inflammation. Myoglobinuria was demonstrated in the kidney by immunohistochemistry. Degeneration of neurons throughout the whole brain was also evident, in addition to haemorrhagic foci in the pons and medulla. Serious bronchopneumonia was also found in the right lung. These findings provide evidence that oral intake of MDMA can result in cardiotoxicity, inducing cardiac arrhythmia and cardiovascular collapse. As a consequence of the compromised blood supply, brain necrosis may occur, followed by severe bronchopneumonia. Ingestion of MDMA could also lead to liver damage as well as myoglobinuria resulting from rhabdomyolysis. These data suggest that death in this case had been caused largely by MDMA intoxication.

Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the direct effect of myoglobin on renal tubules and isolated kidney mitochondria while measuring mitochondrial respiratory control, production of reactive oxygen and nitrogen species and lipid peroxidation. In parallel, we evaluated mitochondrial damage under myoglobinurea in vivo. An increase of lipid peroxidation products in kidney mitochondria and release of cytochrome c was detected on the first day of myoglobinuria. In mitochondria incubated with myoglobin we detected respiratory control drop, uncoupling of oxidative phosphorylation, an increase of lipid peroxidation products and stimulated NO synthesis. Mitochondrial pore inhibitor, cyclosporine A, mitochondria-targeted antioxidant (SkQ1) and deferoxamine (Fe-chelator and ferryl-myoglobin reducer) abrogated these events. Similar effects (oxidative stress and mitochondrial dysfunction) were revealed when myoglobin was added to isolated renal tubules. Thus, rhabdomyolysis can be considered as oxidative stress-mediated pathology with mitochondria to be the primary target and possibly the source of reactive oxygen and nitrogen species. We speculate that rhabdomyolysis-induced kidney damage involves direct interaction of myoglobin with mitochondria possibly resulting in iron ions release from myoglobin's heme, which promotes the peroxidation of mitochondrial membranes. Usage of mitochondrial permeability transition blockers, Fe-chelators or mitochondria-targeted antioxidants, may bring salvage from this pathology.

We describe an 18-year-old man with muscle cramps and recurrent exertional myoglobinuria, without hemolytic anemia or brain dysfunction. Phosphoglycerate kinase (PGK) deficiency was documented in muscle and erythrocytes and molecular analysis of the PGK1 gene identified a novel mutation, T378P. This is the ninth case presenting with isolated myopathy, whereas most other patients show hereditary non-spherocytic hemolytic anemia alone or associated with brain dysfunction, and a few patients have myopathy plus brain involvement. Although the diverse tissue involvement in PGK deficiency remains unclear, all mutations in myopathic patients tend to cluster in the C terminal domain, adjacent to the substrate-binding pocket. This may lead to a failure in the closure of the N terminal and C terminal domains and loss of stability due to lack of inter-domain communication during the catalytic process.

Bilateral leg compartment syndrome due to myonecrosis caused by inappropriate use of statins is a rare but potentially fatal complication of this lipid lowering medication. We report a case of a 39-year-old woman who presented with suspicious critical lower limb ischemia. Subsequently, bilateral leg compartment syndrome and myonecrosis developed. The primary cause of myonecrosis was due to misuse of simvastatin mistaken by the patient for a weight-reducing drug. Urgent fasciotomies were performed and the patient underwent urgent renal replacement therapy with continuous hemodialysis for acute renal failure due to myoglobinuria. After this complex treatment, the patient was discharged. She almost fully recovered with only a residual paresis of the left fibular nerve. According to literature, this is a unique case of bilateral compartment syndrome and myonecrosis with acute renal failure due to statin overdose leading to acute renal failure and bilateral fasciotomy.

Mutations in the FKRP gene may be associated with cardiac involvement. The aim of our study was to assess myocardial involvement in patients with LGMD2I, using physical examination, echocardiography, resting and 24-h ambulatory electrocardiogram and cardiac magnetic resonance imaging, with particular attention to the detection of myocardial morphologic abnormalities. Patients were compared to matched controls. Twenty-three patients were enrolled (men 10--women 13; 32.3+/-9.5 years). Twenty-two had the C826A gene mutation (homozygous 12, heterozygous 10). Nine patients had severe muscle alterations, 10 had milder muscle involvement and 4 had isolated exertional myoglobinuria. When compared to controls, LGMD2I patients had reduced left ventricular ejection fraction (50.8+/-13.9 versus 66.6+/-3.8%, p

Mutations in the caveolin-3 gene (CAV3) can lead to a broad spectrum of clinical phenotypes. Phenotypes that have so far been associated with primary caveolin-3 deficiency include limb girdle muscular dystrophy, rippling muscle disease, distal myopathy and hyperCKaemia. This is the first report describing the clinical, pathological and genetic features of patients with caveolinopathy from the UK. Ten patients (six families) were identified via the National Commissioning Group (NCG) service for patients with limb girdle muscle dystrophy in Newcastle. Myalgia was the most prominent symptom in our cohort of patients and for 50% it was the reason for referral. Muscle weakness was only found in 60% of the patients, whereas rippling muscle movement was present in 80%. One of the patients reported episodes of myoglobinuria and another one episodes of hypoglycaemia. Five different mutations were identified, two of which were novel and three that had previously been described. Caveolinopathy needs to be considered as a differential diagnosis in a range of clinical situations, including in patients who do not have any weakness. Indeed, rippling muscles are a more frequent symptom than weakness, and can be detected in childhood. Presentation with myalgia is common and management of it as well as of myoglobinuria and hypoglycaemia may have a major impact on the patients' quality of life.

A 55-year-old man was hospitalized for endovascular stent placement in both right common iliac and femoral arteries for relief of claudication symptoms due to peripheral vascular disease. Angiography demonstrated diffuse atherosclerosis of the infrarenal aorta and severe stenosis of the right common iliac and right femoral arteries. Physical examination showed diminished but palpable peripheral pulses. Uncomplicated stent placement was done in the right common iliac and right femoral arteries via a left femoral artery approach resulting in improved pedal pulses. Over the next 36 hours, the patient developed severe bilateral lower extremity pain followed by extensive livedo reticularis over lower extremities, elevated creatine kinase levels, myoglobinuria, and a rise in serum creatinine to 1.5 mg/dL (133 micromol/L). Pedal pulses continued to be palpable. This was followed by bilateral lower extremity compartment syndrome, requiring fasciotomies. Myoglobinuria cleared with hydration and creatinine kinase levels returned to normal; however, the patient ultimately developed gangrene of both lower extremities. Bilateral below the knee amputations were performed and histopathology showed wide spread cholesterol crystals in arterioles and small and medium sized arteries in skin and muscle of both lower extremities. This case emphasizes the potential for major complications of cholesterol embolism associated with even uncomplicated vascular procedures performed for treatment of peripheral vascular disease.

Carnitine palmitoyltransferase II (CPT II) deficiency is the most common inherited disorder of lipid metabolism characterized in its adult form by attacks of myalgia and myoglobinuria. We analyzed a cohort of 22 CPT II-deficient patients (representing 20 independent probands) to correlate clinical presentation and molecular data. The common p.Ser113Leu mutation was detected with an allelic frequency of 67.5% (27/40), in association with mild adult-onset phenotype. In addition to the p.Ser113Leu mutation, other 10 disease-causing mutations were identified, 5 of which were novel. They are a micro-insertion within exon 5, three aminoacid substitutions within the coding region, namely p.Arg151Trp, p.Asp576Gly, p.Arg247Trp and a truncating stop codon mutation (p.Arg554Ter). Our data expand the spectrum of CPT II mutations and help to evaluate possible correlations between genotypes and phenotypes.

Biochemical defects in the respiratory chain are mostly associated with deficiencies in Complexes I, III and IV, caused by nuclear or mitochondrial DNA mutations. Combined defects including Complex II have been reported very rarely and have muscular symptoms as the main manifestation, including muscle weakness, exercise intolerance and myoglobinuria. We report a patient with a fatal progressive myopathy and muscle biopsy showing diffuse reduction in succinate dehydrogenase activity, ragged red fibers and intense lipid accumulation. Cytochrome c oxidase (COX) histochemistry demonstrated 30% of fibers with increased subsarcolemmal staining while 27% were COX negative. Western blotting analysis showed reduction in the expression of the 39 kDa subunit of Complex I, subunit II of Complex IV and the 70 kDa subunit of Complex II. Our findings suggest that the patient had a complex pattern of mitochondrial dysfunction affecting multiple respiratory chain complexes (I, II and IV) and fatty acid metabolism. This report adds a new histological pattern associated to combined deficiencies of respiratory chain with involvement of Complex II and shows that this disease may be fatal with a rapid progression.

A 13-year old Thoroughbred cross gelding (528 kg) underwent lameness investigation. Because of his temperament, general anesthesia was required to facilitate ultrasound of the left fore fetlock and intra-articular medication of three joints. Anesthesia was induced with ketamine/diazepam after acepromazine/detomidine premedication. Anesthesia was maintained for 40 minutes with a guaifenesin/detomidine/ketamine intravenous infusion. Recovery from anesthesia was initially uneventful, although of a moderate duration (70 minutes). Once standing, the horse proceeded to box walk in an agitated state and became recumbent on two occasions. The horse was manually restrained, at which time its rectal temperature was 41.8°C. Cooling measures were employed (fans, ice-water enemas, wet rugs, intravenous fluid therapy (IVFT), and topical application of surgical spirit) until rectal temperature reached 38.7°C. IVFT was continued for a further 16 hours. Four days after recovery from anesthesia, bilateral triceps, deltoideus, trapezius, and rhomboideus muscle swelling was observed. Blood creatinine kinase was elevated (24,898 IU/L). Treatment for postanesthetic myopathy was initiated (hot packing of the muscle groups, topical dimethylsulfoxide [DMSO] cream application, and oral phenylbutazone). Myoglobinuria was not observed at any time. Muscle swelling decreased over the following 3 days. The horse was discharged on day 11 and has since returned to work.

Intravenous infusion of norepinephrine is usually effective and safe to maintain adequate cerebral perfusion pressure for the management of posttraumatic intracranial hypertension. We report the case of a 17-year-old woman who suffered from traumatic intracranial bleeding and hypotension; she developed rhabdomyolysis, myoglobinuria and acute renal failure after receiving high dose norepinephrine postoperatively. Hemodialysis was begun 3 days after the onset of myoglobinuria when acute renal failure was noted, despite aggressive fluid supplementation and alkaline diuresis. After aggressive treatment and dialysis, the patient's myoglobinuria and rhabdomyolysis gradually declined. Her kidneys eventually regained normal function. We consider that systemic hypotension may have been the leading cause for development of rhabdomyolysis, and vasoconstrictors such as norepinephrine aggravated this. We emphasise the potentially devastating consequences of rhabdomyolysis when a large dose of norepinephrine is given for the treatment of hypotension during cerebral perfusion pressure-guided management.

A 45-year-old male patient had an episode of acute renal failure with myoglobinuria, myalgias, weakness, and markedly increased serum CK levels. Similar episodes had occurred in the past. Carnitine palmitoyl-transferase II (CPT II) deficiency was documented both biochemically and genetically. Interestingly, muscle biopsy also showed some ragged red fibers (RRF) and complete mitochondrial DNA (mtDNA) sequence disclosed a homoplasmic T3394C point mutation. This mutation is described in Leber's hereditary optic neuropathy (LHON) or in patients with diabetes mellitus.

Sauna-related burns are rare, even in Finland where sauna bathing is a popular leisure pastime. Burns induced by hot air are even more rare and constitute a very small subgroup of all sauna burns. Hot air burns are characterised by a combination of full thickness skin damage with deep tissue destruction. We report here on six consecutive patients suffering from hot air sauna burns with rhabdomyolysis. All six patients were middle-aged, the majority of them men. Acute excessive consumption of alcohol exacerbated by a hot environment resulted in dehydration and loss of consciousness. Immobility and prolonged exposure to hot, dry air resulted in third degree regional burns with 5–32% TBSA. Rhabdomyolysis was evident on admission. The laboratory values of plasma creatine kinase (P-CK), plasma myoglobin (PM), blood pH, and serum potassium (S-K) during the first five days were evaluated. Aggressive fluid management and correction of acidosis and myoglobinuria were started on admission. Surgical management consisted of early, aggressive excision at fascial level, in some patients involving sacrifice of the upper layers of muscle. Even so, mortality in this small series was 50%. The best indicator of poor prognosis was a highly elevated CK value on the second post-injury day.

Rhabdomyolysis-induced myoglobinuric acute renal failure accounts for about 10-40% of all cases of acute renal failure (ARF). Nitric oxide and reactive oxygen intermediates play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). This study was designed to investigate the effect of molsidomine and L-arginine in glycerol induced ARF in rats. Six groups of rats were employed in this study, group I served as control, group II was given 50% glycerol (8 ml/kg, intramuscularly), groups III and IV were given glycerol plus molsidomine (5 mg/kg, and 10 mg/kg p.o. route respectively) 60 min prior to the glycerol injection, group V animals were given glycerol plus L-arginine (125 mg/kg, p.o.) 60 min prior to the glycerol injection, and group VI received L-NAME (10 mg/kg, i.p.) along with glycerol 30 min prior to glycerol administration. Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of catalase, reduced glutathione and superoxide dismutase. Tissue and urine nitrite levels were measured as an index of total nitric oxide levels. Glycerol treatment resulted in a marked decrease in tissue and urine nitric oxide levels, renal oxidative stress and significantly deranged the renal functions along with deterioration of renal morphology. Pre-treatment of animals with molsidomine (10 mg/kg) and L-arginine 60 min prior to glycerol injection markedly attenuated fall in nitric oxide levels, renal dysfunction, morphological alterations, reduced elevated TBARS and restored the depleted renal antioxidant enzymes. The animals treated with L-NAME along with glycerol further worsened the renal damage observed with glycerol. As a result, our results indicate that molsidomine and L-arginine may have beneficial effects in myoglobinuric ARF.

The term PRIS—propofol infusion syndrome— was originally coined by Bray in 1998 to describe the adverse effects associated with the use of propofol in the paediatric population. PRIS was defined as acute refractory bradycardia leading to asystole in the presence of one or more of the following: metabolic acidosis (base excess of 210 mmol litre), rhabdomyolysis or myoglobinuria, lipaemic plasma, or enlarged liver or fatty liver. Although first described in the paediatric population, it has been increasingly reported in adult intensive care patients, particularly in neurointensive care. The safe dose of propofol infusion for sedation in intensive care is considered to be 1–4 mg kg h, but fatal cases of PRIS have been reported after infusion doses as low as 1.9–2.6 mg kg h as well, promoting the idea that genetic factors may have a role to play.

Background Carnitine palmitoyltransferase II (CPT II) deficiency is one of the most common disorders of oxidative fatty acid metabolism. In this disorder, long-chain acylcarnitines cannot be converted to acyl CoA and there is impairment of β-oxidation of fatty acids. Results In the 3 distinct clinical subtypes of CPT II deficiency, adult onset myopathic form shows mild clinical manifestations, characterized by recurrent rhabdomyolysis after intense physical stress. In this study, we report a case with adult myopathic form of CPT II deficiency presenting recurrent exercise-induced myoglobinuria. Conclusion The acylcarnitine profile showed characteristic CPTII deficiency profile and sequencing of the CPT2 gene showed 2 novel missense mutations p. H369Q and p G497S.