Manganism Explained

Manganism
Diagnosis:- determination of the concentration of manganese in the blood- biochemical blood test: determination of the activity of ALT, ACT, LDH, creatine phosphokinase (CPK);- indicators of protein metabolism,- concentrations of thyroid hormones.Instrumental research.EEG, CT, MRI, global EMG, ENMG data are evaluated.In the early stages determine - the speed of motor and sensory reactions, the rate of attention, the amount of short-term memory, in later stages - productive memory, verbal-logical thinking, the level of personal and reactive anxiety, depression, neuroticism

Manganism or manganese poisoning is a toxic condition resulting from chronic exposure to manganese.[1] It was first identified in 1837 by James Couper.[2]

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 micrograms Mn/m3 can lead to manganese-induced symptoms.[3]

In initial stages of manganism, neurological symptoms consist of reduced response speed, irritability, mood changes, and compulsive behaviors.[4] 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.

Causes

Welding

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). [5] [6] [7]

Illicit methcathinone manufacturing

Manganism is also documented in reports of illicit methcathinone manufacturing.[8] This is due to manganese being a byproduct of methcathinone synthesis if potassium permanganate is used as an oxidiser.[9] 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.[10]

Drinking water, fuel additive, Maneb, paint and steelmaking

Reports also mention such sources as contaminated drinking water,[11] and fuel additive methylcyclopentadienyl manganese tricarbonyl (MMT),[12] which on combustion becomes partially converted into manganese phosphates and sulfate that go airborne with the exhaust,[13] [14] [15] and manganese ethylene-bis-dithiocarbamate (Maneb), a pesticide.[16] 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.

Pathophysiology

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.[17] The exact neurotoxic mechanism of manganese is uncertain but there are clues pointing at the interaction of manganese with iron,[18] [19] [20] [21] zinc,[22] aluminum,[22] and copper. Based on a number of studies, disturbed iron metabolism could underlie the neurotoxic action of manganese.[23] 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.[24] [25]

It participates in Fenton reactions and could thus induce oxidative damage, a hypothesis corroborated by the evidence from studies of affected welders.[26] A study of the exposed workers showed that they have significantly fewer children.[27] 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.[28]

Treatment

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,[29] [30] [31] but the response to treatment goes down after 2 or 3 years,[32] with worsening condition of the same patients noted even after 10 years since last exposure to manganese.[33] 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.[34] [35]

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.[3]

Epidemiology

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.[36]

See also

Further reading

Notes and References

  1. Book: Daiana. Silva Avila. Robson. Luiz Puntel. Michael. Aschner. Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. 13. 2013. Springer. 199–227. Chapter 7. Manganese in Health and Disease. 10.1007/978-94-007-7500-8_7. 24470093. 6589086. 978-94-007-7499-5 .
  2. Couper . J. . Sur les effets du peroxide de manganèse . Journal de chimie médicale, de pharmacie et de toxicologie . 1837 . 3 . 223–5 .
  3. 10.1111/j.1471-4159.2009.06534.x . Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation . 2010 . Yin . Zhaobao . Jiang . Haiyan . Lee . Eun-Sook Y. . Ni . Mingwei . Erikson . Keith M. . Milatovic . Dejan . Bowman . Aaron B. . Aschner . Michael . Journal of Neurochemistry . 112 . 5 . 1190–8 . 20002294 . 2819584.
  4. Roth JA . Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination . Biol. Res. . 39 . 1 . 45–57 . 2006 . 16629164 . 10.4067/S0716-97602006000100006. free .
  5. Fryzek JP, Hansen J, Cohen S, Bonde JP, Llambias MT, Kolstad HA, Skytthe A, Lipworth L, Blot WJ, Olsen JH . A cohort study of Parkinson's disease and other neurodegenerative disorders in Danish welders . Journal of Occupational and Environmental Medicine . 47 . 5 . 466–72 . May 2005 . 10.1097/01.jom.0000161730.25913.bf . 15891525 . 29870690 .
  6. 10.1136/oem.2005.022921. 135–40 . Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders . 2006 . Fored . C M . Occupational and Environmental Medicine . 63 . 2 . 16421393 . Fryzek . JP . Brandt . L . Nise . G . Sjögren . B . McLaughlin . JK . Blot . WJ . Ekbom . A . 2078076.
  7. Marsh GM, Gula MJ . Employment as a welder and Parkinson disease among heavy equipment manufacturing workers . Journal of Occupational and Environmental Medicine . 48 . 10 . 1031–46 . October 2006 . 10.1097/01.jom.0000232547.74802.d8 . 17033503 . 1355456 .
  8. de Bie RM, Gladstone RM, Strafella AP, Ko JH, Lang AE . Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse . . 64 . 6 . 886–9 . June 2007 . 17562938 . 10.1001/archneur.64.6.886 .
  9. Sanotsky, Y., Lesyk, R., Fedoryshyn, L., Komnatska, I., Matviyenko, Y. and Fahn, S.. Manganic encephalopathy due to "ephedrone" abuse . . 22 . 9. 1337–1343 . June 2007 . 17566121 . 10.1002/mds.21378. 11564105 .
  10. 10.1093/jat/9.1.45 . 45–46 . Bazooka: Cocaine-Base and Manganese Carbonate . Journal of Analytical Toxicology . 1985 . 9 . 1 . J. G. . Ensing . 3981975.
  11. 10.1080/00039896.1989.9935883. 2751354 . 175–178 . Possible Health Effects of High Manganese Concentration in Drinking Water . 1989 . Kondakis . Xenophon G. . Makris . Nicolas . Leotsinidis . Michael . Prinou . Mary . Papapetropoulos . Theodore . Archives of Environmental Health . 44 . 3.
  12. 10385898. 379–397 . 1999 . Hudnell . HK . Effects from environmental manganese exposures: A review of the evidence from non-occupational exposure studies . 20 . 2–3 . Neurotoxicology.
  13. 10385878. 145–150 . 1999 . Lynam . DR . Roos . JW . Pfeifer . GD . Fort . BF . Pullin . TG . Environmental effects and exposures to manganese from use of methylcyclopentadienyl manganese tricarbonyl (MMT) in gasoline . 20 . 2–3 . Neurotoxicology.
  14. Reynolds JG, Roos JW, Wong J, Deutsch SE. Manganese particulates from vehicles using MMT fuel. In 15th International Neurotoxicology Conference, Little Rock, AR, 1997.
  15. 10.1016/0048-9697(90)90098-F . 107–114 . Environmental assessment of MMT™ fuel additive . 1990 . Lynam . D.R. . Pfeifer . G.D. . Fort . B.F. . Gelbcke . A.A. . Science of the Total Environment . 93 . 2113712. 1990ScTEn..93..107L .
  16. 10.1212/WNL.38.4.550 . 550–553 . Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication . 1988 . Ferraz . H. B. . f. Bertolucci . P. H. . Pereira . J. S. . Lima . J.G.C. . f. Andrade . L. A. . Neurology . 38 . 4 . 3352909. 20400188 .
  17. Book: Ballatori, N. . 12. Molecular mechanisms of hepatic metal transport . Zalups . R.K. . Koropatnick . J. . Molecular Biology and Toxicology of Metals . Taylor & Francis . 2000 . 0748407987 . 346–381 .
  18. 10385907 . 489–497 . 1999 . Verity . MA . Manganese neurotoxicity: A mechanistic hypothesis . 20 . 2–3 . Neurotoxicology.
  19. 10.1016/S0006-8993(01)02049-2 . 175–9 . Iron overload following manganese exposure in cultured neuronal, but not neuroglial cells . 2001 . Zheng . Wei . Zhao . Qiuqu . Brain Research . 897 . 11282372 . 1–2. 3980869 .
  20. 10.1016/S0006-8993(99)01558-9 . 125–132 . Alteration of iron homeostasis following chronic exposure to manganese in rats . 1999 . Zheng . Wei . Zhao . Qiuqu . Slavkovich . Vesna . Aschner . Michael . Graziano . Joseph H . Brain Research . 833 . 10375687 . 4126166 . 1.
  21. 10.1081/CLT-100108512. Neurotoxicology of the Brain Barrier System: New Implications . 711–719 . 2001 . Zheng . Wei . Clinical Toxicology . 39 . 7 . 11778669 . 4111935.
  22. 10385902 . 433–444 . 1999 . Lai . JC . Minski . MJ . Chan . AW . Leung . TK . Lim . L . Manganese mineral interactions in brain . 20 . 2–3 . Neurotoxicology.
  23. 10.1016/S0006-8993(98)00481-8 . 334–342 . Manganese inhibits mitochondrial aconitase: A mechanism of manganese neurotoxicity . 1998 . Zheng . Wei . Ren . Sean . Graziano . Joseph H. . Brain Research . 799 . 2 . 9675333. 4126159 .
  24. Manganese-driven CoQ deficiency . Nature Communications . 2022 . 10.1038/s41467-022-33641-x . 36229432 . 9563070 . Diessl . Jutta . Berndtsson . Jens . Broeskamp . Filomena . Habernig . Lukas . Kohler . Verena . Vazquez-Calvo . Carmela . Nandy . Arpita . Peselj . Carlotta . Drobysheva . Sofia . Pelosi . Ludovic . Vögtle . F.-Nora . Pierrel . Fabien . Ott . Martin . Büttner . Sabrina . 13 . 1 . 6061 . 2022NatCo..13.6061D .
  25. Web site: Masterjohn . Chris . Manganese Toxicity is a CoQ10 Deficiency . 11 March 2024 . 11 March 2024.
  26. Li G, Zhang L, Lu L, Wu P, Zheng W . Occupational exposure to welding fume among welders: alterations of manganese, iron, zinc, copper, and lead in body fluids and the oxidative stress status . J. Occup. Environ. Med. . 46 . 3 . 241–8 . 2004 . 10.1097/01.jom.0000116900.49159.03 . 15091287 . 4126160.
  27. 10.1002/ajim.4700070208 . 171–176 . Fertility of male workers exposed to mercury vapor or to manganese dust: A questionnaire study . American Journal of Industrial Medicine . 1985 . 7 . 2 . Robert . Lauwerys . 3976664.
  28. 10.1002/tera.1420520207 . 109–115 . Developmental toxicity of mangafodipir trisodium and manganese chloride in Sprague-Dawley rats . 1995 . Treinen . Kimberley A. . Gray . Tim J. B. . Blazak . William F. . Teratology . 52 . 2 . 8588182.
  29. 10.1001/archneur.57.4.597 . 597–599 . Manganese Intoxication . 2000 . Lee . J.-W. . Archives of Neurology . 57 . 4 . 10768639.
  30. Mena I, Court J, Fuenzalida S, Papavasiliou PS, Cotzias GC . Modification of chronic manganese poisoning. Treatment with L-dopa or 5-OH tryptophane . N Engl J Med . 282 . 1 . 5–10 . 1970 . 10.1056/NEJM197001012820102 . 5307796.
  31. Rosenstock HA, Simons DG, Meyer JS . Chronic manganism. Neurologic and laboratory studies during treatment with levodopa . JAMA . 217 . 10 . 1354–8 . 1971 . 10.1001/jama.217.10.1354 . 4998860.
  32. 10.1212/WNL.43.8.1479 . 1479–83 . Progression after chronic manganese exposure . 1993 . Huang . C.-C. . Lu . C.-S. . Chu . N.-S. . Hochberg . F. . Lilienfeld . D. . Olanow . W. . Calne . D. B. . Neurology . 43 . 8 . 8351000. 12621501 .
  33. 10.1212/WNL.50.3.698 . 698–700 . Long-term progression in chronic manganism: Ten years of follow-up . 1998 . Huang . C.-C. . Chu . N.-S. . Lu . C.-S. . Chen . R.-S. . Calne . D. B. . Neurology . 50 . 3 . 9521259. 34347615 .
  34. 10.1016/S0022-510X(02)00111-9 . 93–96 . Myoclonic involuntary movement associated with chronic manganese poisoning . 2002 . Ono . Kenjiro . Komai . Kiyonobu . Yamada . Masahito . Journal of the Neurological Sciences . 199 . 12084450 . 1–2. 40327454 .
  35. 7936278 . 1583–1586 . 1994 . Calne . DB . Chu . NS . Huang . CC . Lu . CS . Olanow . W . Manganism and idiopathic parkinsonism: Similarities and differences . 44 . 9 . Neurology . 10.1212/WNL.44.9.1583. 28563940 .
  36. Web site: Groundwater Pollution Red River Delta/Vietnam . 2011 . Eawag — Swiss Federal Institute of Aquatic Science and Technology .
    Winkel LH, Pham TK, Vi ML, Stengel C, Amini M, Nguyen TH, Pham HV, Berg M . Arsenic pollution of groundwater in Vietnam exacerbated by deep aquifer exploitation for more than a century . Proc Natl Acad Sci U S A . 108 . 4 . 1246–51 . 2011 . 10.1073/pnas.1011915108 . 21245347 . 3029707. free .

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