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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restless legs syndrome (RLS) is a neurologic movement disorder that is often associated with a sleep complaint. Patients with RLS have an irresistible urge to move their legs, which is usually due to disagreeable sensations that are worse during periods of inactivity and often interfere with sleep. It is estimated that between 2 and 15 percent of the population may experience symptoms of RLS. Primary RLS likely has a genetic origin. Secondary causes of RLS include iron deficiency, neurologic lesions, pregnancy and uremia. RLS also may occur secondarily to the use of certain medications. The diagnosis of RLS is based primarily on the patient's history. A list of questions that may be used as a basis to assess the likelihood of RLS is included in this article. Pharmacologic treatment of RLS includes dopaminergic agents, opioids, benzodiazepines and anticonvulsants. The primary care physician plays a central role in the diagnosis and management of RLS.
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PMID:Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome. 1127 42

Iron is a vitally important element in mammalian metabolism because of its unsurpassed versatility as a biologic catalyst. However, when not appropriately shielded or when present in excess, iron plays a key role in the formation of extremely toxic oxygen radicals, which ultimately cause peroxidative damage to vital cell structures. Organisms are equipped with specific proteins designed for iron acquisition, export, transport, and storage as well as with sophisticated mechanisms that maintain the intracellular labile iron pool at an appropriate level. These systems normally tightly control iron homeostasis but their failure can lead to iron deficiency or iron overload and their clinical consequences. This review describes several rare iron loading conditions caused by genetic defects in some of the proteins involved in iron metabolism. A dramatic decrease in the synthesis of the plasma iron transport protein, transferrin, leads to a massive accumulation of iron in nonhematopoietic tissues but virtually no iron is available for erythropoiesis. Humans and mice with hypotransferrinemia have a remarkably similar phenotype. Homozygous defects in a recently identified gene encoding transferrin receptor 2 lead to iron overload (hemochromatosis type 3) with symptoms similar to those seen in patients with HFE-associated hereditary hemochromatosis (hemochromatosis type 1). Transferrin receptor 2 is primarily expressed in the liver but it is unclear how mutant forms cause iron overload. Mutations in the gene encoding the iron exporter, ferroportin 1, cause iron overload characterized by iron accumulation in macrophages yet normal plasma iron levels. Plasma iron, together with dominant inheritance, discriminates iron overload due to ferroportin mutations (hemochromatosis type 4) from hemochromatosis type 1. Heme oxygenase 1 is essential for the catabolism of heme and in the recycling of hemoglobin iron in macrophages. Homozygous heme oxygenase 1 deletion in mice leads to a paradoxical accumulation of nonheme iron in macrophages, hepatocytes, and many other cells and is associated with low plasma iron levels, anemia, endothelial cell damage, and decreased resistance to oxidative stress. A similar phenotype occurred in a child with severe heme oxygenase 1 deficiency. Recently, a mutation in the L-subunit of ferritin has been described that causes the formation of aberrant L-ferritin with an altered C-terminus. Individuals with this mutation in one allele of L-ferritin have abnormal aggregates of ferritin and iron in the brain, primarily in the globus pallidus. Patients with this dominantly inherited late-onset disease present with symptoms of extrapyramidal dysfunction. Mice with a targeted disruption of a gene for iron regulatory protein 2 (IRP2), a translational repressor of ferritin, misregulate iron metabolism in the intestinal mucosa and the central nervous system. Significant amounts of ferritin and iron accumulate in white matter tracts and nuclei, and adult IRP2-deficient mice develop a movement disorder consisting of ataxia, bradykinesia, and tremor. Mutations in the frataxin gene are responsible for Friedreich ataxia, the most common of the inherited ataxias. Frataxin appears to regulate mitochondrial iron (or iron-sulfur cluster) export and the neurologic and cardiac manifestations of Friedreich ataxia are due to iron-mediated mitochondrial toxicity. Finally, patients with Hallervorden-Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2). The cardinal feature of this extrapyramidal disease is pathologic iron accumulation in the globus pallidus. The defect in PANK2 is predicted to cause the accumulation of cysteine, which binds iron and causes oxidative stress in the iron-rich globus pallidus.
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PMID:Rare causes of hereditary iron overload. 1238

Iron is essential for oxidation-reduction catalysis and bioenergetics; however, unless appropriately shielded, this metal plays a crucial role in the formation of toxic oxygen radicals that can attack all biological molecules. Organisms are equipped with specific proteins designed for iron acquisition, export and transport, and storage, as well as with sophisticated mechanisms that maintain the intracellular labile iron pool at an appropriate level. Despite these homeostatic mechanisms, organisms often face the threat of either iron deficiency or iron overload. This review describes several hereditary iron-overloading conditions that are confined to the brain. Recently, a mutation in the L-subunit of ferritin has been described that causes the formation of aberrant L-ferritin with an altered C-terminus. Individuals with this mutation in one allele of L-ferritin have abnormal aggregates of ferritin and iron in the brain, primarily in the globus pallidus. Patients with this dominantly inherited late-onset disease present with symptoms of extrapyramidal dysfunction. Mice with a targeted disruption of a gene for iron regulatory protein 2 (IRP2), a translational repressor of ferritin, misregulate iron metabolism in the intestinal mucosa and the central nervous system. Significant amounts of ferritin and iron accumulate in white matter tracts and nuclei, and adult IRP2-deficient mice develop a movement disorder consisting of ataxia, bradykinesia, and tremor. Mutations in the frataxin gene are responsible for Friedreich's ataxia, the most common of the inherited ataxias. Frataxin appears to regulate mitochondrial iron-sulfur cluster formation, and the neurologic and cardiac manifestations of Friedreich's ataxia are due to iron-mediated mitochondrial toxicity. Patients with Hallervorden-Spatz syndrome, an autosomal recessive, progressive neurodegenerative disorder, have mutations in a novel pantothenate kinase gene (PANK2). The cardinal feature of this extrapyramidal disease is pathologic iron accumulation in the globus pallidus. The defect in PANK2 is predicted to cause the accumulation of cysteine, which binds iron and causes oxidative stress in the iron-rich globus pallidus. Finally, aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused by loss-of-function mutations in ceruloplasmin gene that leads to misregulation of both systemic and central nervous system iron trafficking. Affected individuals suffer from extrapyramidal signs, cerebellar ataxia, progressive neurodegeneration of retina, and diabetes mellitus. Excessive iron depositions are found in the brain, liver, pancreas, and other parenchymal cells, but plasma iron concentrations are decreased. These conditions are not common, but awareness about them is important for differential diagnosis of various neurodegenerative disorders.
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PMID:Hereditary causes of disturbed iron homeostasis in the central nervous system. 1510 72

Restless legs syndrome (RLS) is a poorly understood sleep-related movement disorder which can be primary or associated with other conditions, most commonly iron deficiency, uremia and peripheral nerve disease. We present a case of RLS with an unusual secondary cause: primary hyperparathyroidism with hypercalcemia. This patient experienced complete and sustained relief of RLS symptoms immediately after parathyroidectomy, with normalization of her serum parathyroid hormone (PTH) and calcium levels. Early recognition and treatment of this uncommonly detected underlying cause is important because it is potentially curative in this frequently disabling condition for which usually only symptomatic treatment is available.
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PMID:Restless legs syndrome associated with primary hyperparathyroidism. 1585 61

Restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) are considered to be a continuum of a neurological sleep disorder associated with abnormal iron metabolism or deficiency. I describe a case of RLS and PLMD in a cystic fibrosis patient with iron deficiency from chronic hemoptysis. This is the first case that reports RLS and PLMD manifesting from iron deficiency caused by chronic hemoptysis in advanced cystic fibrosis lung disease.
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PMID:Restless leg syndrome manifested by iron deficiency from chronic hemoptysis in cystic fibrosis. 1698 19

Evidence for tissue iron deficiency in restless legs syndrome (RLS) is limited to the substantia nigra (SN). Using MRI, we assessed T2 values of various brain regions in 6 RLS patients and 19 controls and correlated them with sonographically assessed SN echogenicity. Both neuroimaging features are supposed to correlate with tissue iron content. Mean T2 values of all regions were higher in patients (2.9-7.8%), though significantly increased only in four regions; the mean T2 over all voxels was higher in patients (5.1%, P < 0.001) and correlated inversely with SN echogenicity (r = -0.61, P < 0.001). This indicates multiregional (global) brain iron deficiency in RLS and proposes SN echogenicity as a potential morphological marker for brain iron status. (c) 2008 Movement Disorder Society.
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PMID:Multiregional brain iron deficiency in restless legs syndrome. 1844 25

Restless Legs Syndrome (RLS) has been recognized as a common and treatable neurologic disorder in adults for some time, but the occurrence of RLS in children and adolescents has seen relatively delayed acceptance. A large, population-based study has recently reported a 1.9% and 2% prevalence of RLS in children and adolescents, respectively. RLS in children is closely associated with periodic limb movement disorder (PLMD), and symptoms of both may range from mild to severe. An early, accurate diagnosis of RLS or PLMD provides substantial benefits to an individual's quality of life, especially in cases of poor-sleep related intellectual or emotional dysfunction. Treatment plans should use emerging knowledge of how RLS and PLMD affect children and adolescents to correctly identify these disorders and aim to reduce or eliminate symptoms. Best-fitting therapy will consider severity of symptoms, comorbid conditions, and phenotypic variables. Promising progress has been made in understanding the genetic components of RLS as well as the role of iron deficiency in exacerbating symptoms. A review of current research on RLS and PLMD in children and adolescents is presented.
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PMID:Restless legs syndrome and periodic limb movement disorder in children and adolescents. 1855 95

Restless legs syndrome is a common neurologic movement disorder that affects approximately 10 percent of adults. Of those affected with this condition, approximately one third have symptoms severe enough to require medical therapy. Restless legs syndrome may be a primary condition, or it may be secondary to iron deficiency, renal failure, pregnancy, or the use of certain medications. The diagnosis is clinical, requiring an urge to move the legs usually accompanied by an uncomfortable sensation, occurrence at rest, improvement with activity, and worsening of symptoms in the evening or at night. Restless legs syndrome causes sleep disturbances, is associated with anxiety and depression, and has a negative effect on quality of life. Treatment of secondary causes of restless legs syndrome may result in improvement or resolution of symptoms. Currently, there is little information regarding the effects of lifestyle changes on the symptoms of restless legs syndrome. If medications are needed, dopamine agonists are the primary medications for moderate to severe restless legs syndrome. Other medications that may be effective include gabapentin, carbidopa/levodopa, opioids, and benzodiazepines.
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PMID:Restless legs syndrome. 1869 9

Restless legs syndrome (RLS) is a common movement disorder wherein sensory motor symptoms are observed in the limbs mainly during sleep and quiet wakefulness. The diagnostic criteria for RLS were established in 1995 by the International RLS Study Group (IRLSSG) and revised in 2003. The prevalence of RLS in Europe and North America was reported to be between 5% and 12%. On the other hand, the prevalence of RLS in Asia was lesser than that in Europe and North America: it was estimated to be less than 4%. This difference might be associated with vacial, cultural, and language differences. Genetic factors are known to contribute to the etiology of RLS in up to two-thirds of these patients. Furthermore, RLS might complicate an already existing medical condition. The development of secondary RLS is associated with renal failure, iron deficiency, frequent blood donation, Parkinson disease, neuropathy, as well as pregnancy. Generally, these medical condition are more frequently complicated in patient with RLS than in healthy controls. However, there is no conclusive evidence to prove an association between these medical conditions and RLS. Genetic contribution, environmental factors and other covariates such as gender, age, iron deficiency, as well as medical conditions play an important role in the development of RLS. In conclusion, epidemiological evidence suggests that both the primary and secondary forms of RLS are common neurological disorders. Future epidemiological studies are required to determine the potential risk factors contributing to the development of this disorder.
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PMID:[Prevalence of restless legs syndrome]. 1951 11

Iron is essential in the brain, yet too much iron can be toxic. Tight regulation of iron in the brain may involve intrinsic mechanisms that control internal homeostasis independent of systemic iron status. Iron abnormalities occur in various neurological disorders, usually with symptoms or neuropathology associated with movement impairment or behavioral disturbances rather than cognitive impairment or dementia. Consistent with this, polymorphisms in the HFE gene, associated with the iron overload disorder hemochromatosis, show stronger associations with the movement disorder amyotrophic lateral sclerosis (motor neuron disease) than with cognitive impairment. Such associations may arise because certain brain regions involved in movement or executive control are particularly iron-rich, notably the basal ganglia, and may be highly reliant on iron. Various mechanisms, including iron redistribution causing functional iron deficiency, lysosomal and mitochondrial abnormalities or oxidative damage, could underlie iron-related neuropathogenesis. Clarifying how iron contributes causatively to neurodegeneration may improve treatment options in a range of neurodegenerative disorders. This review considers how modern molecular genetic approaches can be applied to resolve the complex molecular systems and pathways by which brain iron homeostasis is regulated and the molecular changes that occur with iron dyshomeostasis and neuropathogenesis.
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PMID:Molecular genetic approaches to understanding the roles and regulation of iron in brain health and disease. 2034 52


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