Metabolic myopathies are inborn errors of metabolism that result in impaired energy production due to defects in glycogen, lipid, mitochondrial, and possibly adenine nucleotide metabolism. Myopathies can be classified as hereditary or acquired. Metabolic myopathies are mendelian inherited disorders with marked phenotypic and genotypic heterogeneity due to defects in energy metabolism. Frontiers stepwise approach to myopathy in systemic disease. Onset birththird decade or over a period of several years. Statin drugs are being used more and more frequently, with up to 29. See individual gene test descriptions for information on clinical features, molecular biology of gene products and spectra of pathogenic variants. Pdf congenital and metabolic myopathies of childhood or. Metabolic myopathies present with either permanent fixed or episodic abnormalities, such as weakness, wasting, exerciseintolerance, myalgia, or an increase of muscle breakdown.
Mitochondrial myopathy with lactic acidosis genetic and. A different kind of metabolic myopathy caused by acid maltase deficiency is called pompe disease. The metabolic myopathies are a heterogeneous group of disorders that share the common feature of inadequate production of cellular energy in the muscle. Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal. Muscle diseases can constitute a large variety of both acquired and hereditary disorders.
Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug and toxininduced, critical illness myopathy, metabolic, and myopathies with other systemic disorders. Muscular dystrophies and acquired myopathies are inflammatory and non inflammatory. Introduction have examined an association between a metabolic myo metabolic myopathies are common disorders that are pathy and polyarteritis nodosa. On the other hand, the dynamic myopathies are associated with exercise intolerance i. They include var ious mitochondrial myopathies, glycogen storage dis case presentation eases and disorders of purine metabolism 1,2. Tips for diagnosing metabolic myopathies the rheumatologist. Although some experts have considered myoadenylate deaminase deficiency to be part of the group of metabolic myopathies,2,3 it is not directly involved in intermediary metabolism, and its role in causing a metabolic defect in muscle is seriously questioned. Myalgia, like fatigue, is another nonspecific symptom of some myopathies see table 3. Have you been searching the internet for sites that offer nelson textbook of pediatrics 21st edition pdf download free. The metabolic myopathies are a heterogeneous group of disorders caused by defects in muscle energy metabolism that cause inadequate production or maintenance of atp levels. Metabolic myopathies are a heterogeneous group of disorders characterized by mostly inherited defects of enzymatic pathways involved in muscle cell metabolism. Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle.
The metabolic abnormality was mcardle disease in 1 patient, mitochondrial myopathy in 1, mucolipidosis type ii in 1, and undefined in 3. Metabolic diseases of muscle muscular dystrophy association. Metabolic myopathies are a clinically and genetically heterogeneous group of disorders caused by defects in cellular muscle metabolism resulting in muscle weakness, recurrent myoglobinuria, and exercise intolerance. They include glycogen storage disorders, defects of lipid metabolism, and mitochondrial diseases. Metabolic myopathies in spanish espanol download printfriendly pdf. Metabolic myopathy an overview sciencedirect topics. Metabolic myopathies have varying levels of symptoms, being most severe when developed during infancy. Thus, in the appropriate clinical context, normal edx studies do not necessarily rule out the presence of a myopathy. Mar 17, 2020 disease definition muscle phosphoglycerate mutase deficiency pgamd is a metabolic myopathy characterised by exerciseinduced cramp, myoglobinuria, and presence of tubular aggregates in the muscle biopsy. Myalgias may be episodic metabolic myopathies or nearly constant inflammatory muscle disorders. Login to your account pdf 63 kbdownload pdf 63 kb save. Myopathy evaluation and diagnosis kirsten gruis, md 2010 page 1 of 19 i. Cartoon representation of the molecular jutasa of protein registered with 1bq3 code. Inborn errors of energy metabolism associated with myopathies.
Metabolic myopathies american college of rheumatology. Michio hirano md, in neurobiology of disease, 2007. Patients with metabolic myopathies have an underlying deficiency of energy metabolism in muscle that may be the. Metabolic myopathies are a diverse group of inherited biochemical diseases involving limitation of the use of fuels by skeletal muscle to generate energy. Positive symptoms associated with myopathies may include myalgias, cramps, contractures, myotonia, or myoglobinuria. Metabolic myopathies are genetic disorders, predominantly inherited in an autosomal recessive manner and typically caused by severe loss of function of an enzyme.
Approach to patients with neuromuscular disease aaem. Metabolic myopathies comprise a diverse group of inborn errors of intermediary metabolism affecting skeletal muscle, and often present clinically as an inability to perform normal exercise. Pdf metabolic myopathy presenting with polyarteritis. Congenital myopathies chronic, slowly progressive systemic myopathy late onset, acute or sub acute endocrine myopathies adult onset, acute or sub acute. However, recurrent rhabdomyolysis is often genetic in nature. Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. These diseases can be categorized as disorders of lipid metabolism, glycogen and glucose metabolism, or mitochondrial myopathies that impair both lipid and glucose metabolism. However, myalgias, the most frequent sideeffect, occur in up to 7% of patients. Genetic testing for metabolic myopathy and rhabdomyolysis. Common symptoms include muscle weakness, cramps, stiffness, and tetany. Of 6 cases of metabolic myopathy, 3 had a normal emg. Metabolic myopathies can also be viewed as static or dynamic disorders. Patients may present with indolent myopathic features, exercise intolerance or recurrent rhabdomyolysis. Metabolic myopathies may present in different stages of life and can be difficult to diagnose.
The first five chapters describe the clinical approach to the patients who are suspected of having a metabolic myopathy, and summarize the role and the range of findings that may be seen with electromyography, muscle biopsy and magnetic resonance spectroscopy, and the normal response of skeletal muscle during exercise. Test metabolic myopathies, rhabdomyolysis and exercise. Patients with mitochondrial myopathies mm or myophosphorylase deficiency mcardles disease, mca show impaired capacity for o 2 extraction, low maximal aerobic power, and reduced exercise tolerance. These myopathies are typically subdivided into three. Jan 01, 2010 metabolic myopathy in childhood is an uncommon entity. Metabolic myopathy and rhabdomyolysis panel plus referring healthcare professional name hospital patient name dob gender primary sample type age 28 sample collection date order id customer sample id summary of results primary findings the patient is heterozygous for cpt2 c. In patients who have deteriorating strength, it is important to make note of whether the rate of progression is over days, weeks, months, or years. Myopathies pdf myopathies are classified as either inherited or acquired. Citations references 100 figures 4 abstract and figures. Different forms of metabolic myopathies are distinguished by which enzyme is deficient or missing.
The genetic causes for rhabdomyolysis include metabolic myopathy, disorders of intramuscular calcium release, mitochondrial disorders and muscular dystrophies. In two identical twins, 18yearold girls, 4 however, the main symptom was not weakness, but muscle cramps provoked by exercise and, more significantly, by a highfat, lowcarbohydrate dietcircumstances suggesting that the disease was a metabolic myopathy, and that the clue to its cause had to be looked for in the faulty utilization of fatty. The degree of exercise intolerance in the metabolic myopathies varies greatly between disorders and even from one individual to the next within a disorder. Those who do not develop a form of a metabolic myopathy until they are in their young adult or adult life tend to have more treatable symptoms that can be helped with a change in diet and exercise. Xlinked myotubular myopathy and duchenne muscular dystrophy. May 29, 2020 a first group of metabolic myopathies that includes mad absent, glycogenoses, and mitochondrial myopathy exhibits a large increase in. Early recognition of these primary metabolic myopathies is essential to help prevent disease morbidity and mortality from rhabdomyolysis. Nelson textbook of pediatrics 21st edition pdf free download.
For instance, mcardle disease is due to a lack of enzyme that assists in carbohydrate metabolism. At the cellular level, metabolic myopathies lack some kind of enzyme that prevent the chemical reactions necessary to create adenosine triphosphate atp. However, their diagnosis often remains a challenge. Symptoms typically include exertional fatigue, cramping, myalgia and myoglobinuria which usually occur during periods of high energy. Pdf metabolic myopathy presenting with polyarteritis nodosa. This is the first study to demonstrate that skeletal muscle from patients with chf is characterized by a unique transcriptome signature that underpins an upper and lower limb metabolic myopathy closely linked to worse symptoms. Would you like to get nelson textbook of pediatrics 21st edition pdf download.
The metabolic myopathies are genetically heterogeneous. Sep 17, 2019 when evaluating patients with possible myopathic symptoms, rheumatologists must consider a rare, but important, group of inherited disorders. We hope this report will heighten awareness of common metabolic myopathies that may present later in life. The investigation and management of metabolic myopathies. Apart from the manual muscle testing for muscle strength, the examination of. Impaired oxygen extraction in metabolic myopathies. Diagnostic delays are common and clinicians need a high index of suspicion t. Two eminently treatable genetic metabolic myopathies. The investigation and management of metabolic myopathies j clin pathol. Metabolic myopathies are a heterogeneous group of disorders characterized by mostly inherited defects of enzymatic. They are generally genetic defects that interfere with muscles ability to create energy. Pdf the recognition of a series of metabolicenzymatic dysfunction in metabolic myopathies has allowed new. Glycogenstorage disease type ii gsdii, also referred to as pompes disease, is a rare storage disorder presenting as metabolic myopathy with multiorgan dysfunction. The majority are inherited in an autosomal recessive ar manner, though autosomal dominant ad and xlinked xl disorders are also included.
Gtr test id help each test is a specific, orderable test from a particular laboratory, and is assigned a unique gtr accession number. Edx studies are most useful to diagnose a myopathy when further data are needed. The typical manifestations of a metabolic myopathy are exerciseinduced myalgias, exercise intolerance, and cramps. Patients suffering from metabolic myopathies due to compromised energy metabolism may present with exercise. Exercise efficiency impairment in metabolic myopathies. The static myopathies are defined by the presence of fixed or progressive weakness. Exercise efficiency impairment in metabolic myopathies scientific. Metabolic myopathies renaissance school of medicine at stony. Definitive diagnosis was made by muscle biopsy, biochemical analysis, and genetic testing of the muscle tissue.
Unique transcriptome signature distinguishes patients with. Inherited metabolic myopathy and hemolysis due to a mutation in aldolase a. Metabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system resulting in exercise. Individuals with a metabolic myopathy frequently present with progressive exercise intolerance, muscle weakness, and cramps, but a wide spectrum of. Muscle mri and muscle biopsy play important roles in patients with exercise intolerance and dyspnea when metabolic myopathy is suspected. Fatty acid oxidation defects faod, glycogen storage disease, and mitochondrial myopathies represent the 3 mai. Transaminitis and skeletal myotoxicity, with elevated serum creatine kinase ck. Diagnostic delays are common and clinicians need a high index of suspicion to recognise and differentiate metabolic myopathies from other conditions that present in a. Other metabolic myopathies with massive lipid storage and weakness are. Metabolic myopathies mm are rare inherited primary muscle disorders that are mainly due to abnormalities of muscle energy metabolism resulting in skeletal muscle dysfunction. About metabolic myopathy and rhabdomyolysis rhabdomyolysis is a medical condition in which damaged striated skeletal muscles break down easily and rapidly. Some end products of this lysis, such as myoglobin, are toxic to kidneys and may cause acute renal failure.
In our set up it was the commonest metabolic myopathy encountered. Metabolic myopathy presenting with polyarteritis nodosa. Metabolic myopathies are a group of genetic muscular diseases resulting from defective metabolism affecting primarily muscles. Major recent advances in the field of metabolic myopathies have helped delineate the genetic and biochemical basis of these disorders. Metabolic myopathies occasionally precipitated acutely, may be progressive, fixed or recurrent. June 2000 congenital a n d metabolic myopathies of childhood or adult onset oscar mir6, montserrat laguno, ferran masanes, milagrosa perea, alvaro urbanomrquez, and josep m. It also speculates on the potential relationship between metabolic myopathy and systemic vasculitis. Metabolic myopathies comprise a clinically etiological diverse group of disorders caused by defects in cellular energy metabolism.
Two eminently treatable genetic metabolic myopathies yee wc. Myopathy evaluation and diagnosis kirsten gruis, md 2010. Metabolic myopathy and rhabdomyolysis panel tests gtr. Information about the progression of the disease process is very important in helping to classify the specific etiology of myopathy. Myopathies in systemic disease results from several different disease processes including endocrine, inflammatory, paraneoplastic, infectious, drug and toxininduced, critical illness myopathy, metabolic, collagen related, and myopathies with other systemic disorders. Myopathies pdf myopathies pdf myopathies pdf download. Apr 17, 2020 metabolic myopathies are a heterogeneous group of disorders characterized by mostly inherited defects of enzymatic pathways involved in muscle cell metabolism. Blueprint genetics metabolic myopathy and rhabdomyolysis panel. Pdf metabolic myopathies mm are rare inherited primary muscle disorders that are mainly due to abnormalities of. Authors simon edward olpin 1, elaine murphy 2, richard james kirk 3, robert william taylor 4, rosaline quinlivan 5 affiliations 1 department of clinical chemistry, sheffield. Muscular dystrophies, congenital myopathies, myotonias, channelopathies periodic paralysis, metabolic and mitochondrial myopathies 2. They include glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders. Metabolic myopathies are a clinically and etiologically heterogeneous group of disorders due to defects in muscular energy metabolism. Metabolic myopathies discovered during investigations of statin.
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