[McArdle's disease revealed by acute low back pain]. / Une maladie de McArdle révélée par une lombalgie aiguë.

INTRODUCTION: McArdle disease, or glycogen storage disease type V (GSD 5), is a rare metabolic myopathy linked to an autosomal recessive myophosphorylase deficiency. CASE REPORT: We report the case of a 17-year-old male patient who was referred to the emergency department for the management of acute inflammatory low back pain, without traumatic context, associated with an increase of CK at 66,336 UI/L (N<192UI/L) and a CRP at 202mg/L. The immunological assessment was negative and the spinal MRI showed images in favor of necrotizing fasciitis affecting the erector spinae muscles, among others. Faced with the description of difficulties in practicing physical activities since childhood and a non-ischaemic forearm exercise test showing no elevation in lactacidemia, genetic tests were carried out, finding two heterozygous variants in the PYGM gene: c.1963G>A (p.Glu655Lys) class 5 and c.2178-1G>A class 4, confirming the diagnosis of McArdle disease. DISCUSSION: GSD 5 is a disease characterized essentially by muscular fatigability during exercise. The case reported here is original in the clinical circumstances leading to the diagnosis, i.e., inaugural acute low back pain with rhabdomyolysis. This symptomatology had already been described before, but in a patient whose diagnosis was already known. Spinal MRI showed non-specific muscle inflammation and necrosis. Muscle biopsy only found necrosis but no pathological elements typical of the diagnosis. If the symptoms are suggestive, it may be preferable to directly perform a non-ischaemic forearm exercise test, in order to go directly to molecular genetic analysis. There is no specific curative treatment of GSD 5. However, some measures can be implemented to limit the symptoms, such as learning physical exercises, limiting intense efforts and adopting dietary recommendations.

Fatigue and associated factors in 172 patients with McArdle disease: An international web-based survey.

McArdle disease is an autosomal recessive inherited disease caused by pathogenic variants in the PYGM gene, resulting in virtual absence of the myophosphorylase enzyme in skeletal muscle. Patients experience physical activity intolerance, muscle pain, and muscle fatigue. This study aimed to investigate other fatigue domains with the Multidimensional Fatigue Inventory (MFI-20) along with an investigation of potential contributing factors, including relevant disease and lifestyle-related factors. We conducted a survey in an international cohort of patients with McArdle disease. The survey included questions on demographics and McArdle disease-related symptoms, and the questionnaires: MFI-20, Insomnia Severity Index (ISI), and International Physical Activity Questionnaire Short-Form (IPAQ-SF). One hundred seventy-four responses were included in the data analyses. We found relatively high fatigue scores in all five domains (general fatigue (12.9 ± 2.2), mental fatigue (10.1 ± 4.1), physical fatigue (13.7 ± 4.1), reduced activity (12.1 ± 4.1), and reduced motivation (10.4 ± 3.4)). Fatigue associated with McArdle symptom severity (p < 0.005), lower levels of physical activity (assessed by IPAQ-SF) (p < 0.05), and poor sleep (assessed by ISI) (p < 0.05). These findings call for clinical focus and future research into fatigue, sleep and mental health in patients with McArdle disease.

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.

Rhabdomyolysis in McArdle disease caused by scuba diving.

McArdle disease is a glycogen storage disease that results in rhabdomyolysis during intense exercise. A number of different triggers have been described. We evaluated a patient with McArdle disease who presented with rhabdomyolysis after recreational scuba diving. There was no concern for barotrauma or decompression sickness. His symptoms resolved with standard-of-care management for non-diving-related rhabdomyolysis. Features of his experience provoked questions about the diving-related factors contributing to his presentation. We present the case and explore possible mechanisms of diving-related injury in patients with McArdle disease, including the possible effects of hyperoxia, hyperbaria, hypothermia and strenuous activity.

A first in literature: anesthesia management in kidney transplant surgery of a patient with McArdle disease.

McArdle disease is an inherited myopathy that autosomal recessive inheritance and is also known as glycogen storage disease type 5. Myoglobinuria, increase in serum CK level and darkening of urine color secondary to myoglobinuria are typical. Patients may have symptoms associated with increased rhabdomyolysis secondary acute renal failure or hyperkalemia after long and strenuous exercise periods. Today, many studies in the literature have shown that transplantation is superior to dialysis in patients with end-stage renal disease. Our case is a 53-year-old male patient with the diagnosis of McArdle syndrome who was going to have a kidney transplant. The patient had essential hypertension and history of HBsAg+. Total intravenous anesthesia technique was chosen as the anesthesia technique because inhaled anesthetic agents may trigger malignant hyperthermia in the patient. We didn't experience any perioperative complications in our patient. In conclusion, renal transplantation performed with total intravenous in a McArdle syndrome patient may be a simple and effective technique.

[Rhabdomyolysis of rare etiology]. / Rhabdomyolyse mit seltener Ursache.

A 40-year-old Syrian man presented to the emergency department with a 5-day history of anuria. He had previously excreted dark urine. Major rhabdomyolysis and crush kidney were found, meaning that hemodialysis was immediately initiated. A detailed patient history in the patient's mother tongue revealed indications of metabolic myopathy. The PYGM-associated glycogen storage disease type V (McArdle disease) was confirmed by next generation sequencing panel diagnostics. The most important treatment approach is to avoid rhabdomyolysis through only moderate physical exertion.

Cardiac arrest as a manifestation of unknown Type V glycogenosis: a case report.

Few cases have been reported to date, in which a massive rhabdomyolysis causes a cardiac arrest in a male adult suffering from undiagnosed McArdle disease. Veno-arterial extracorporeal membrane oxygenation and cytokine adsorption filter (CytoSorb®) were required to reach a complete and successful recovery.

McArdle disease in a patient with anorexia nervosa: a case report.

BACKGROUND: McArdle disease is an autosomal recessive genetic disorder caused by a deficiency of the glycogen phosphorylase (myophosphorylase) enzyme, which muscles need to break down glycogen into glucose for energy. Symptoms include exercise intolerance, with fatigue, muscle pain, and cramps being manifested during the first few minutes of exercise, which may be accompanied by rhabdomyolysis. CASE PRESENTATION: This case report describes for the first time the clinical features, diagnosis and management of a 20 year-old patient with anorexia nervosa and McArdle disease, documented by means of muscle biopsy. CONCLUSION: Anorexia nervosa and McArdle disease interact in a detrimental bidirectional way. In addition, some laboratory parameter alterations (e.g., elevated values of creatine kinase) commonly attributed to the specific features of eating disorders (e.g., excessive exercising) may delay the diagnosis of metabolic muscle diseases. On the other hand, the coexistence of a chronic disease, such as McArdle disease, whose management requires the adoption of a healthy lifestyle, can help to engage patients in actively addressing their eating disorder.

Rhabdomyolysis Episode in an Individual with McArdle's Disease after Low Aerobic Exercise.

McArdle's disease, known as blockage of muscle glycogen metabolism, is characterized by glycogen accumulation of chains in skeletal striated muscles. One of the typical symptoms of the disease is the feeling of intolerance to exercise. Severe muscle cram and contracture, which often cause stiffness, occur due to a lack of muscle energy substrate during the exercise. These factors can lead to muscle damage, myoglobinuria, and, in severe cases, renal failure and rhabdomyolysis. Rhabdomyolysis is a syndrome that presents injury and necrosis of muscle cells leading to the release of intracellular material to the circulatory system. The present study aimed to report rhabdomyolysis in an individual with McArdle's disease after exercise of walking with low intensity. Patient, aged 33 years, was treated in the emergency room of a hospital located in the State of Rio de Janeiro, Brazil. After performing a full lap on the block of home (~500 m in ~4 min 37 s), walking at a moderate speed (~6.5 km/h), the individual felt sick and was rescued, later being hospitalized. The examinations collected presented hematocrit (HCT) compatible with chronic disease anemia and myoglobinuria. The patient was discharged from the intensive care center on the 3rd day, after a 45% drop in creatine kinase. The patient described in the present study achieved full recovery. Attention to symptoms, early diagnosis, and immediate treatment made it possible to interrupt the development of complications caused by rhabdomyolysis, not allowing progression to acute renal failure.

Clinical Presentation and Management of Severe Acute Renal Failure in McArdle Disease.

McArdle disease, also known as glycogen storage disease type V, is an autosomal recessive disease due to the absence of myophosphorylase activity, leading to the complete disruption of glycogen breakdown in muscles. We present a rare case of a Caucasian male, aged 26 years, who developed rhabdomyolysis-induced acute renal failure and uremic encephalopathy. Neurological examination and histopathological studies supported the diagnosis of McArdle disease. The severity of his symptoms necessitated urgent hemodialysis, upon which the patient reported improvement in status. Acute renal failure in McArdle disease usually resolves with supportive treatment and maintenance of regular physical activity. Nevertheless, in more severe cases, intensive care with urgent hemodialysis may be needed. A multidisciplinary approach is necessary for the adequate management of similar cases.

When POTS is the tip of the iceberg: Rare cases of dysautonomia as a possible manifestation of another disorder.

BACKGROUND: Postural tachycardia syndrome (POTS) is a heterogenous disorder of the autonomic nervous system that is commonly associated with small fiber neuropathy, Ehlers-Danlos Syndrome and autoimmune disorders, but association with rare conditions may also occur. METHODS: Reported here are clinical features, diagnostic tests and treatment outcomes of 6 unique patients who presented with POTS and were subsequently diagnosed with Fabry disease, McArdle disease, Complex V mitochondrial disease, carcinoid tumor, Hodgkin's lymphoma and chemotherapy-induced neuropathy. RESULTS: All patients (age range 15-57 years, 3 females, 3 males) presented with orthostatic intolerance of at least 6 months duration, and all patients had co-morbid small fiber neuropathy. Five patients presented with symptoms of POTS months to years before the underlying or associated medical condition was discovered, and three out of six patients experienced either complete resolution or significant improvement of POTS after treatment of the underlying or associated medical condition. CONCLUSION: In rare cases, POTS can present as a possible manifestation of genetic, neoplastic or neurotoxic disorders. Unusual clinical features that fall outside of the typical spectrum of dysautonomia can point toward the presence of another disorder and help guide further diagnostic investigation.

RETINAL DYSTROPHY IN A PATIENT WITH McARDLE DISEASE.

PURPOSE: To report a case of pattern dystrophy in a patient with McArdle disease, a rare autosomal recessive disorder of glycogen metabolism. METHODS: Case report. RESULTS: A 29-year-old woman with a history of muscle biopsy-confirmed McArdle disease presented with fundus findings consistent with pattern dystrophy. Multimodal imaging, including optical coherence tomography and fundus autofluorescence, was performed. CONCLUSION: To our knowledge, this is the third reported case of pattern dystrophy in a patient with McArdle disease.

Repeatedly in Rhabdomyolysis.

ABSTRACT: Repeated presentations of a rare symptom in a patient should make a physician stop and evaluate for rare conditions. This is a report of a teenager with multiple episodes of rhabdomyolysis and weakness. He was eventually diagnosed as having McArdle muscular dystrophy, or glycogen storage disease type V. His rhabdomyolysis has been severe, with a creatinine kinase level of >320,000 U/L, myoglobinuria, transaminitis, and elevated bilirubin. He has a low threshold for triggering rhabdomyolysis, such as doing an hour of aerobic exercise 2 days in a row. McArdle disease is a glycogen storage disorder in which the skeletal muscle cannot convert glycogen to glucose. Unlike other glycogen storage disorders, McArdle muscular dystrophy only affects the skeletal muscle, sparing the brain and visceral organs, leading to a vague phenotype. These patients have exercise intolerance, muscle cramps, and rhabdomyolysis. Many patients report loading with simple carbohydrates before exercise, as they have learned that this can increase their stamina. The vague symptoms can lead to decades of delay in diagnosis and significant mismanagement. Rhabdomyolysis is the most dangerous sign of McArdle disease, and it can lead to acute kidney injury, resulting in renal failure requiring dialysis in the severest cases.Rhabdomyolysis has numerous causes, but when it is recurrent, especially with seemingly insignificant triggers, one needs to develop a broader differential and pursue advanced testing. This testing can include specific exercise tests, genetic sequencing, and muscle biopsy. This case report will guide the clinician through the process of evaluating recurrent rhabdomyolysis, working through the differential diagnosis and testing options.1.

An elderly diabetic patient with McArdle disease and recurrent rhabdomyolysis: a potential association with late hypoinsulinemia?

BACKGROUND: McArdle disease is a myopathy caused by mutations in PYGM gene that is characterized by reduced or absent activity of myophosphorylase. Reports of patients with concomitant McArdle disease and diabetes are scarce. We report a case of a patient with a late diagnosis of McArdle disease and we postulate that symptoms may be related to hypoinsulinemia. CASE PRESENTATION: This report describes the evolution of an elderly diabetic patient with confirmed diagnosis of McArdle's disease based on the absence of myophosphorylase activity in the analysis of muscle biopsy, and a homozygous mutation in the PYGM gene. The variant - Chr11: 64.525 (p. Asn168*fs) has not been previously described. The diagnosis of McArdle disease was confirmed after two episodes of rhabdomyolysis, at 77 and 81 years of age, as the symptoms were, until then, discrete. The "second-wind phenomenon" was not spontaneously reported, but it was confirmed when directly questioned. We postulate that the later episodes of rhabdomyolysis occurred because of a progressive decrease in insulin production with a consequent reduction in the uptake of blood glucose by muscle cells, thus compromising the cellular energy balance. To our knowledge, this is the first report of recurrent rhabdomyolysis in an elderly diabetic patient with genetically proven McArdle disease. Our initial attempt to reduce insulin resistance with metformin and pioglitazone was not effective, possibly because of inadequate insulinemia. However, an improvement was evident after the administration of low doses of intermediate-acting insulin. CONCLUSIONS: In view of the patient's clinical evolution, we suggest the use of medication that reduces insulin resistance for patients with McArdle disease and type 2 diabetes, pre-diabetes or even normoglycemic metabolic syndrome.

The potential of a ketogenic diet to minimize effects of the metabolic fault in glycogen storage disease V and VII.

PURPOSE OF REVIEW: To explore the potential of a low carbohydrate ketogenic diet (LCKD) to counter physical activity intolerance, pain and muscle damage for glycogen storage disease (GSD) V and VII, and highlight the realistic possibility that nutrition could be key. RECENT FINDINGS: Carbohydrate (CHO) ingestion during physical activity in GSDV and a LCKD for GSDVII is common. For the latter, a long-term study demonstrated improvement in physiological markers while on a LCKD. This included improvement in aerobic power and activity tolerance. In GSDV, preliminary research on a LCKD suggest a diet of 75% fat, 15% protein, 10% CHO, is best for improved function and compliance. Ketones provide immediate fuel for acute physical activity, and have an epigenetic role, improving ketone and lipid use. Evidence from elite athletes found a LCKD can increase fat oxidation and is optimal at 70% VO2max. This suggests the need to also improve conditioning via exercise to maximize the benefit of a LCKD. SUMMARY: A high CHO diet in GSDV and VII comes with a restricted physical activity capacity alongside significant pain, muscle damage and risk of renal failure. Mounting evidence suggests a LCKD is efficacious for both disorders providing an immediate fuel source which may negate the need for a 'warm-up' prior to every activity and restore 'normal' function.

Longitudinal case study and phenotypic multimodal characterization of McArdle disease-linked retinopathy: insight into pathomechanisms.

Background: We present a longitudinal clinical characterization of PYGM-linked pattern dystrophy in an adult male patient.Materials and Methods: A patient affected by McArdle disease (glycogen storage disease type V) and homozygous for the nonsense variant PYGM c.148C>T p.(Arg50*) underwent ophthalmic examinations over a 9-year-interval, including fundus photography, fundus autofluorescence, optical coherence tomography (OCT), OCT-angiography and electroretinography (ERG).Results: At age 52, the patient was asymptomatic but yellow flecks were first observed in the macula of both eyes. This yellow flecks at the posterior pole progressed towards a pattern-like dystrophy over a 5-year-period. By fundus autofluorescence imaging the appearance of new hyperautofluorescent flecks and the extension of existing ones was observed over time. Concomitantly, a slow progression of the size of atrophic areas was seen at the posterior pole. Scotopic ERGs were within normal limits, but photopic Flicker responses were decreased, indicating reduced cone function.Conclusions: This additional case of PYGM-linked pattern dystrophy further confirms retinopathy as a clinical phenotype associated with McArdle disease. PYGM expression pattern suggests a disease mechanism involving impaired glycogen metabolism both in the retinal pigment epithelium and in cone photoreceptors.

Can hyperuricemia predict glycogen storage disease (McArdle's disease) in rheumatology practice? (Myogenic hyperuricemia).

Gout disease is an inflammatory arthritis that arises due to the accumulation of monosodium urate crystals (MSU) around the joints and in tissues. Clinical manifestation of metabolic diseases leading to secondary hyperuricemia most predominantly occurs in the form of gouty arthritis. Hyperuricemia and gout may develop during the course of glycogen storage diseases (GSD), particularly in GSD type I, which involves the liver. On the other hand, during the course of GSD type V (GSDV, McArdle's disease), which merely affects the muscle tissue due to the deficiency of the enzyme myophosphorylase, hyperuricemia and/or gout is rarely an expected symptom. These patients may mistakenly be diagnosed as having idiopathic hyperuricemia and associated gout, leading to the underlying secondary causes be overlooked and thus, diagnostic delays may occur. In this case report, we present a premenopausal female patient who experienced flare-ups of chronic arthritis while on disease-modifying antirheumatic drugs and intraarticular steroids due to a diagnosis of undifferentiated arthritis. The patient was initially suspected of having gouty arthritis because elevated concentrations of uric acid were incidentally detected, but then, a diagnosis of asymptomatic GSDV was made owing to elevated concentrations of muscle enzymes during colchicine use. Our aims were to remind rheumatologists of the phenomenon of "myogenic hyperuricemia" and to discuss the potential causes of hyperuricemia that develop during GSD along with the available literature.