Manganism
The element manganese in the periodic table
Specialty	Occupational medicine
Diagnostic method	assessment of exposure history presentation of symptoms MRI neurological examination

Manganese poisoning, also called manganism, or Manganese Madness^[1]: 311 is a toxic condition resulting from chronic exposure to manganese.^[2] It was first identified in 1837 by James Couper.^[3]

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 from 1 - 5 mg/m³ can lead to manganese-induced symptoms, but neurotoxicity has been reported with occupational exposure as low as 0.03 mb/m³.^[4]: 1136

In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors.^[5] Upon protracted exposure neurological symptoms are more prominent and resemble those of Parkinson's disease. There are particular differences in both the symptoms and manganese poisoning does not respond levodopa treatment used for Parkinson's disease.^[6]

Manganese poisoning is primarily as consequence of occupational exposure, especially in manganese dioxide mining and smelting. Exposure may also occur during the manufacture of manganese steel, electrical coils, or during the production of potassium permanganate.^[4]

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.^[19] The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron,^{[20][21][22][23]} zinc,^[24] aluminum,^[20][24] and copper.^[24] Based on a number of studies, disturbed iron metabolism could underlie the neurotoxic action of manganese.^[25] 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.^[26][27]

It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders.^[28] A study of the exposed workers showed that they have significantly fewer children.^[29] 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.^[30]

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.^{[citation needed]}

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,^[31][32][33] but the response to treatment goes down after 2 or 3 years,^[34] with worsening condition of the same patients noted even after 10 years since last exposure to manganese.^[35] 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.^[36][37]

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.^[38]

• Alpha synuclein
• Asphalt (disambiguation)
• Concrete
• Joss paper
• Parkinsonism
• Particulates
• Slag
• Slag cement

• Evans, Garrett R.; Masullo, Lawrence N. (2024). "Manganese Toxicity". StatPearls. StatPearls Publishing. PMID 32809738.

• Lucchini, Roberto; Tieu, Kim (30 July 2023). "Manganese-Induced Parkinsonism: Evidence from Epidemiological and Experimental Studies". Biomolecules. 13 (8): 1190. doi:10.3390/biom13081190. PMC 10452806. PMID 37627255. Acute high dose exposure typically causes manganism and the globus pallidus is the primary target. Chronic, low-level exposure extends Mn deposition and toxicity to other brain regions, including the substantia nigra. When combined with other PD-linked gene products such as α-synuclein, parkin, DJ-1, and ATP13A2, it is likely that Mn contributes to the onset and progression of idiopathic PD ... therefore, it is imperative to control this modifiable factor and eliminate all possible causes of overexposure and long-term absorption of low doses.
• Lucchini et al., "Metals and Neurodegeneration" — Research paper on heavy metals poisoning
• Antonini, James M. (2003). "Health Effects of Welding". Critical Reviews in Toxicology. 33 (1): 61–103. doi:10.1080/713611032. PMID 12585507. S2CID 26661513. — Critical review including manganese discussion from National Institute for Occupational Safety and Health (NIOSH)
• "Welding and Manganese Poisoning". Safety Corner. IBEW Journal. July–August 2003. p. 8.
• AWS Study on Welding and Exposure to Manganese^{[permanent dead link]} — Report of an independent study commissioned by the American Welding Society
• Welding Fume Product Liability — Viewpoint of plaintiffs on welding rod litigation
• Welding Rod Litigation Information Network — Viewpoint of defense on welding rod litigation
• Serfozo, Norbert; Lazaridis, Mihalis (December 2023). "Estimation of Particle Emission Rates and Calculation of Human Dose from Arc Welding and Cutting of Stainless Steel in a Simulated Confined Workspace". Aerosol Science and Engineering. 7 (4): 474–487. Bibcode:2023AerSE...7..474S. doi:10.1007/s41810-023-00192-7.
• Steel slag used on rural Iowa roads could be harming children, report shows
• https://www.ncbi.nlm.nih.gov/