Manganism

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Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese.<ref> Template:Cite book </ref> It was first identified in 1837 by James Couper.<ref name="Couper1837">Template:Cite journal</ref>

Signs and symptomsEdit

Chronic exposure to excessive manganese levels can lead to a variety of psychiatric and motor disturbances, termed manganism. Generally, exposure to ambient manganese air concentrations in excess of 5 mg/m³ can lead to manganese-induced symptoms.<ref name="libres.uncg.edu">Template:Cite journal</ref>

In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors.<ref name="pmid16629164">Template:Cite journal</ref> Upon protracted exposure symptoms are more prominent and resemble those of idiopathic Parkinson's disease, as which it is often misdiagnosed, although there are particular differences in both the symptoms; for example, the nature of the tremors, response to drugs such as levodopa, and affected portion of the basal ganglia. Symptoms are also similar to Lou Gehrig's disease and multiple sclerosis.

CausesEdit

WeldingEdit

Manganism has become an active issue in workplace safety as it has been the subject of numerous product liability lawsuits against manufacturers of arc welding supplies. In these lawsuits, welders have accused the manufacturers of failing to provide adequate warning that their products could cause welding fumes to contain dangerously high manganese concentrations that could lead welders to develop manganism. Companies employing welders are also being sued, for what colloquially is known as "welders' disease." However, studies fail to show any link between employment as a welder and manganism (or other neurological problems).Template:Quote needed<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Illicit methcathinone manufacturingEdit

Manganism is also documented in reports of illicit methcathinone manufacturing.<ref name="pmid17562938">Template:Cite journal</ref> This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser.<ref name="pmid17566121">Template:Cite journal</ref> Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic dysarthria. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from cocaine using manganese carbonate.<ref name="bazooka">Template:Cite journal</ref>

Drinking water, fuel additive, Maneb, paint and steelmakingEdit

Reports also mention such sources as contaminated drinking water,<ref name="water">Template:Cite journal</ref> and fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT),<ref name="MMT">Template:Cite journal</ref> which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust,<ref name="MMT2">Template:Cite journal</ref><ref name="MMT3">Reynolds JG, Roos JW, Wong J, Deutsch SE. Manganese particulates from vehicles using MMT fuel. In 15th International Neurotoxicology Conference, Little Rock, AR, 1997.</ref><ref name="MMT4">Template:Cite journal</ref> and manganese ethylene-bis-dithiocarbamate (Maneb), a pesticide.<ref name="maneb">Template:Cite journal</ref> It is found in large quantities in paint and steelmaking processes.

And in very rare cases it can be caused by a defect of the gene SLC30A10.

PathophysiologyEdit

Manganese may affect liver function, but the threshold of acute toxicity is very high. On the other hand, more than 95 percent of manganese is eliminated by biliary excretion. Any existing liver damage may slow this process, increasing its concentration in blood plasma.<ref name="Ballatori2000">Template:Cite book</ref> The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron,<ref name="Verity1999">Template:Cite journal </ref><ref name="Zheng2001">Template:Cite journal</ref><ref name="Zheng1999">Template:Cite journal</ref><ref name="Zheng2001_2">Template:Cite journal</ref> zinc,<ref name="Lai1999">Template:Cite journal</ref> aluminum,<ref name="Verity1999" /><ref name="Lai1999"/> and copper.<ref name="Lai1999" /> Based on a number of studies, disturbed iron metabolism could underlie the neurotoxic action of manganese.<ref>Template:Cite journal</ref> Manganese displaces Iron in the COQ7 hydroxylase enzyme required for coenzyme Q10 synthesis. Supplying CoQ6 (the yeast version of CoQ10) to yeast cells bathed in manganese solution restored mitochondrial function and survival.<ref name="Diessl">Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders.<ref name="Li2004">Template:Cite journal</ref> A study of the exposed workers showed that they have significantly fewer children.<ref name="Lauwerys1985">Template:Cite journal</ref> This may indicate that long-term accumulation of manganese affects fertility. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls.<ref name="Treinen1995">Template:Cite journal</ref>

DiagnosisEdit

Template:Empty section <ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Diagnosis requires a high clinical suspicion alongside recognition of the risk factors placing patients at risk for manganism. Ideal evaluation for the determination of manganese toxicity includes a team-based approach, based on early recognition and outpatient referral to neurology for definitive care. Early consultation with a clinical toxicologist may aid in the identification of the etiology for the patient's symptoms. Usage of MRI or serum-based studies should be done at the request of specialists familiar with toxicity and the latest research

TreatmentEdit

The current mainstay of manganism treatment is levodopa and chelation with EDTA. Both have limited and at best transient efficacy. Replenishing the deficit of dopamine with levodopa has been shown to initially improve extrapyramidal symptoms,<ref name="Lee2000">Template:Cite journal</ref><ref name="Mena1970">Template:Cite journal</ref><ref name="Rosenstock1971">Template:Cite journal</ref> but the response to treatment goes down after 2 or 3 years,<ref name="Huang1993">Template:Cite journal</ref> with worsening condition of the same patients noted even after 10 years since last exposure to manganese.<ref name="Huang1998">Template:Cite journal</ref> Enhanced excretion of manganese prompted by chelation therapy brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment.<ref name="Ono2002">Template:Cite journal</ref><ref name="Calne_etal">Template:Cite journal</ref>

Increased ferroportin protein expression in human embryonic kidney (HEK293) cells is associated with decreased intracellular manganese concentration and attenuated cytotoxicity, characterized by the reversal of manganese-reduced glutamate uptake and diminished lactate dehydrogenase (LDH) leakage.<ref name="libres.uncg.edu"/>

EpidemiologyEdit

The Red River Delta near Hanoi has high levels of manganese and arsenic in the water. Approximately 65 percent of the region’s wells contain high levels of arsenic, manganese, selenium, and barium.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}
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ReferencesEdit

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External linksEdit

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