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Movement Disorders Clinical Practice Oct 2020Movement disorders often emerge from the interplay of complex pathophysiological processes involving the kidneys and the nervous system. Tremor, myoclonus, ataxia,... (Review)
Review
Movement disorders often emerge from the interplay of complex pathophysiological processes involving the kidneys and the nervous system. Tremor, myoclonus, ataxia, chorea, and parkinsonism can occur in the context of renal dysfunction (azotemia and electrolyte abnormalities) or they can be part of complications of its management (dialysis and renal transplantation). On the other hand, myoglobinuria from rhabdomyolysis in status dystonicus and certain drugs used in the management of movement disorders can cause nephrotoxicity. Distinct from these well-recognized associations, it is important to appreciate that there are several inherited and acquired disorders in which movement abnormalities do not occur as a consequence of renal dysfunction or vice versa but are manifestations of common pathophysiological processes affecting the nervous system and the kidneys. These disorders are the emphasis of this review. Increasing awareness of these conditions among neurologists may help them to identify renal involvement earlier, take timely intervention by anticipating complications and focus on therapies targeting common mechanisms in addition to symptomatic management of movement disorders. Recognition of renal impairment in a patient with complex neurological presentation may narrow down the differentials and aid in reaching a definite diagnosis.
PubMed: 33043074
DOI: 10.1002/mdc3.13005 -
Indian Journal of Pathology &... May 2022Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan... (Review)
Review
Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan disorder' status. However, collectively they constitute a relatively common group of disorders that affect not only the skeletal muscle but also the heart, liver, and brain among others. Mitochondrial disorders, with a frequency of 1/8000 population, are the commonest cause of metabolic myopathies. Three main groups that cause metabolic myopathy are glycogen storage disorders (GSD), fatty acid oxidation defects (FAOD), and mitochondrial myopathies. Clinically, patients present with varied ages at onset and neuromuscular features. While newborns and infants typically present with hypotonia and multisystem involvement chiefly affecting the liver, heart, kidney, and brain, patients with onset later in life present with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, GSDs result in high-intensity exercise intolerance while, FAODs, and mitochondrial myopathies predominantly manifest during endurance-type activity, fasting, or metabolically stressful conditions. Evaluation of these patients comprises a meticulous clinical examination and a battery of investigations which includes- exercise stress testing, metabolic and biochemical screening, electrophysiological studies, neuro-imaging, muscle biopsy, and molecular genetics. Accurate and early detection of metabolic myopathies allows timely counseling to prevent metabolic crises and helps in therapeutic interventions. This review summarizes the clinical features, diagnostic tests, pathological features, treatment and presents an algorithm to diagnose these three main groups of disorders.
Topics: Algorithms; Heart; Humans; Infant, Newborn; Metabolism, Inborn Errors; Mitochondrial Myopathies; Muscular Diseases
PubMed: 35562160
DOI: 10.4103/ijpm.ijpm_1088_21 -
Current Neurology and Neuroscience... Oct 2015One large group of hereditary myopathies characterized by recurrent myoglobinuria, almost invariably triggered by exercise, comprises metabolic disorders of two main... (Review)
Review
One large group of hereditary myopathies characterized by recurrent myoglobinuria, almost invariably triggered by exercise, comprises metabolic disorders of two main fuels, glycogen and long-chain fatty acids, or mitochondrial diseases of the respiratory chain. Differential diagnosis is required to distinguish the three conditions, although all cause a crisis of muscle energy. Muscle biopsy may be useful when performed well after the episode of rhabdomyolysis. Molecular genetics is increasingly the diagnostic test of choice to discover the underlying genetic basis.
Topics: Adenosine Triphosphate; Glycogen; Humans; Mitochondria; Muscular Diseases; Myoglobinuria; Renal Dialysis
PubMed: 26319173
DOI: 10.1007/s11910-015-0590-9 -
Cureus Nov 2022Rhabdomyolysis is a pathological condition presenting with symptoms of localized or generalized myalgia and weakness, associated with an increase in serum creatine...
Rhabdomyolysis is a pathological condition presenting with symptoms of localized or generalized myalgia and weakness, associated with an increase in serum creatine kinase level and, often leading to myoglobinuria and acute kidney injury. It has a wide range of etiologies. Immune-mediated necrotizing myopathy (IMNM) is a rare type of inflammatory myopathy, that leads to rhabdomyolysis, and it is divided into three different subtypes: anti-3-hydroxy-3-methylglutaryl-coA reductase (anti-HMGCR, anti-signal recognition particle (anti-SRP), and seronegative. There are slight differences in incidence, age of onset, clinical course, and prognosis between these subtypes. We describe the case of a 67-year-old female with myalgias and weakness of the thighs for six weeks. Laboratory findings showed marked rhabdomyolysis and severe acute kidney injury. The workup led to the diagnosis of seronegative immune-mediated necrotizing myopathy (IMNM) and treatment with corticosteroid and methotrexate was introduced, which led to marked clinical improvement.
PubMed: 36540529
DOI: 10.7759/cureus.31519 -
Biochimica Et Biophysica Acta Apr 2015Metabolic 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... (Review)
Review
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.
Topics: Animals; Electron-Transferring Flavoproteins; Enzyme Replacement Therapy; Glycogen Storage Disease; Humans; Iron-Sulfur Proteins; Lipid Metabolism, Inborn Errors; Muscular Diseases; Oxidoreductases Acting on CH-NH Group Donors
PubMed: 24997454
DOI: 10.1016/j.bbadis.2014.06.031