Manganism or manganese

poison A poison is any chemical substance that is harmful or lethal to living organisms. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figurati ...

ing is a

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

condition resulting from chronic exposure to

manganese Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

. It was first identified in 1837 by James Couper.

Signs and symptoms

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. In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors. Upon protracted exposure symptoms are more prominent and resemble those of

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

, 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 Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...

, and affected portion of the

basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

. Symptoms are also similar to

Lou Gehrig's disease Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lo ...

and

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

Causes

Welding

Manganism has become an active issue in workplace safety as it has been the subject of numerous

product liability Product liability is the area of law in which manufacturers, distributors, suppliers, retailers, and others who make products available to the public are held responsible for the injuries those products cause. Although the word "product" has ...

lawsuits against manufacturers of

arc welding Arc welding is a welding process that is used to join metal to metal by using electricity to create enough heat to melt metal, and the melted metals, when cool, result in a joining of the metals. It is a type of welding that uses a welding power ...

supplies. In these lawsuits,

welders A welder is a person or equipment that fuses materials together. The term welder refers to the operator, the machine is referred to as the welding power supply. The materials to be joined can be metals (such as steel, aluminum, brass, stainles ...

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).

Illicit methcathinone manufacturing

Manganism is also documented in reports of illicit

methcathinone Methcathinone (α-methylamino-propiophenone or ephedrone) (sometimes called "cat" or "jeff" or "catnip" or "M-Kat" or "kat" or "intash") is a monoamine alkaloid and psychoactive stimulant, a substituted cathinone. It is used as a recreational d ...

manufacturing. This is due to manganese being a byproduct of methcathinone synthesis if

potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4. It is a purplish-black crystalline salt, which dissolves in water as K+ and ions to give an intensely pink to purple solution. Potassium permanganate is widely us ...

is used as an oxidiser. Symptoms include apathy, bradykinesia, gait disorder with postural instability, and spastic-hypokinetic

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. It is a condition in which problems effectively occur with the ...

. Another street drug sometimes contaminated with manganese is the so-called "Bazooka", prepared by free-base methods from

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

using manganese

carbonate A carbonate is a salt of carbonic acid, (), characterized by the presence of the carbonate ion, a polyatomic ion with the formula . The word "carbonate" may also refer to a carbonate ester, an organic compound containing the carbonate group ...

Drinking water, fuel additive, Maneb, paint and steelmaking

Reports also mention such sources as contaminated drinking water, and fuel additive

methylcyclopentadienyl manganese tricarbonyl Methylcyclopentadienyl manganese tricarbonyl (MMT or MCMT) is an organomanganese compound with the formula (C5H4CH3)Mn(CO)3. Initially marketed as a supplement for use in leaded gasoline, MMT was later used in unleaded gasoline to increase the oc ...

(MMT), which on

combustion Combustion, or burning, is a high-temperature exothermic redox chemical reaction between a fuel (the reductant) and an oxidant, usually atmospheric oxygen, that produces oxidized, often gaseous products, in a mixture termed as smoke. Combustion ...

becomes partially converted into manganese

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

s and

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

that go airborne with the exhaust,Reynolds JG, Roos JW, Wong J, Deutsch SE. Manganese particulates from vehicles using MMT fuel. In 15th International Neurotoxicology Conference, Little Rock, AR, 1997. and manganese ethylene-bis-dithiocarbamate (

Maneb Maneb (manganese ethylene-bis-dithiocarbamate) is a fungicide and a polymeric complex of manganese with the ethylene bis (dithiocarbamate) anionic ligand. Health effects Exposure to maneb can occur when breathed in; it can irritate the eyes, ...

), a pesticide. It is found in large quantities in

paint Paint is a material or mixture that, when applied to a solid material and allowed to dry, adds a film-like layer. As art, this is used to create an image or images known as a painting. Paint can be made in many colors and types. Most paints are ...

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

SLC30A10 Solute carrier family 30 member 10 is a protein that in humans is encoded by the SLC30A10 gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DN ...

Pathophysiology

Manganese may affect

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

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. The exact

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with

iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...

zinc Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...

aluminum Aluminium (or aluminum in North American English) is a chemical element; it has chemical symbol, symbol Al and atomic number 13. It has a density lower than that of other common metals, about one-third that of steel. Aluminium has ...

, and

copper Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...

. Based on a number of studies, disturbed iron

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

could underlie the neurotoxic action of manganese. Manganese displaces Iron in the COQ7 hydroxylase enzyme required for

coenzyme Q10 Coenzyme Q10 (CoQ10 ), also known as ubiquinone, is a naturally occurring biochemical cofactor (coenzyme) and an antioxidant produced by the human body. It can also be obtained from dietary sources, such as meat, fish, seed oils, vegetables, ...

synthesis. Supplying CoQ6 (the yeast version of CoQ10) to yeast cells bathed in manganese solution restored mitochondrial function and survival. It participates in

Fenton reaction Fenton's reagent is a solution of hydrogen peroxide (H2O2) and an iron catalyst (typically iron(II) sulfate, FeSO4). It is used to oxidize contaminants or waste water as part of an advanced oxidation process. Fenton's reagent can be used to destr ...

s and could thus induce

oxidative damage Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...

, a hypothesis corroborated by the evidence from studies of affected welders. A study of the exposed workers showed that they have significantly fewer children. This may indicate that long-term accumulation of manganese affects

fertility Fertility in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate ...

. Pregnant animals repeatedly receiving high doses of manganese bore malformed offspring significantly more often compared to controls.

Diagnosis

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

Treatment

The current mainstay of manganism treatment is

and

chelation Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

with

EDTA Ethylenediaminetetraacetic acid (EDTA), also called EDTA acid, is an aminopolycarboxylic acid with the formula . This white, slightly water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-solubl ...

. Both have limited and at best transient efficacy. Replenishing the deficit of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

with levodopa has been shown to initially improve

extrapyramidal symptom Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

s, but the response to treatment goes down after 2 or 3 years, with worsening condition of the same patients noted even after 10 years since last exposure to manganese. Enhanced excretion of manganese prompted by

chelation therapy Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medic ...

brings its blood levels down but the symptoms remain largely unchanged, raising questions about efficacy of this form of treatment. 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 Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

uptake and diminished

lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of pyruvic acid, pyruvate to lactic acid, lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that t ...

(LDH) leakage.

Epidemiology

The

Red River Delta The Red River Delta or Hong River Delta () is the flat low-lying plain formed by the Red River and its distributaries merging with the Thái Bình River in Northern Vietnam. ''Hồng'' (紅) is a Sino-Vietnamese word for "red" or "crimson". T ...

near

Hanoi Hanoi ( ; ; ) is the Capital city, capital and List of cities in Vietnam, second-most populous city of Vietnam. The name "Hanoi" translates to "inside the river" (Hanoi is bordered by the Red River (Asia), Red and Black River (Asia), Black Riv ...

has high levels of manganese and

arsenic Arsenic is a chemical element; it has Symbol (chemistry), symbol As and atomic number 33. It is a metalloid and one of the pnictogens, and therefore shares many properties with its group 15 neighbors phosphorus and antimony. Arsenic is not ...

in the water. Approximately 65 percent of the region’s wells contain high levels of arsenic, manganese,

selenium Selenium is a chemical element; it has symbol (chemistry), symbol Se and atomic number 34. It has various physical appearances, including a brick-red powder, a vitreous black solid, and a grey metallic-looking form. It seldom occurs in this elem ...

, and

barium Barium is a chemical element; it has symbol Ba and atomic number 56. It is the fifth element in group 2 and is a soft, silvery alkaline earth metal. Because of its high chemical reactivity, barium is never found in nature as a free element. Th ...

References

External links

{{Poisoning and toxicity Manganese Neurological disorders Toxic effects of metals