Title: Manganese toxicity

 

Key words: manganese, deficiency, toxicity, manganism, poisoning, parenteral nutrition, TPN, cholestatism, basal ganglia, Parkinsonís disease, L-Dopa, cholestasis, †

 

Date: Oct 2006

 

Category:

 

Nutrimed Module:

 

Type: Article

 

Author: Morgan, G

 

Manganese toxicity

Unlike other trace elements, clear evidence of manganese deficiency in clinical practice has not been definitively identified, this in spite of the fact that manganese is essential for the functioning of several key metabolic enzymes such as phosphoenolpyrovate carboxykinase and pyruvate carboxylase (Nielsen 2001). Evidence of toxicity in certain at risk groups has been widely acknowledged, however. Those at risk can be divided into two groups: those exposed to high levels of industrial exposure leading to so-called Ďmanganismí and those unable to excrete accumulating levels of endogenous manganese.

 

1. Industrial manganese toxicity

This has been recognised as a hazard within the metallurgical industry for many years and is caused by exposure to toxic manganese fumes or dust (Couper 1837). Many more recent studies (for example Cotzias 1968, Yamada 1986) have confirmed the original observations of Couper of irreversible neurological damage from manganese poisoning.

 

2. Impaired manganese excretion

Though minor losses occur from the skin, sweat and in the urine, the vast majority of manganese is excreted via the biliary tract. Some control over absorption occurs in the gut but the major homeostatic control mechanism for manganese metabolism remains through biliary excretion. Thus cholestasis and hepatic failure have been associated with accumulation of body manganese and a pathology similar to that of industrial manganese toxicity (Krieger 1995).

 

In recent years prolonged total parenteral nutrition, which is frequently complicated by liver disease (Reynolds 1994), has been associated with similar problems (Mirovitz 1992, Reynolds 1994, Alves 1997). Many of the earlier cases may have been related to inappropriate levels of manganese in the parenteral fluids, a problem which was subsequently addressed. Cases of short-bowel syndrome receiving total parenteral nutrition have also been associated with this syndrome, occasionally without cholestatic features (Ejima 1992). The exact mechanism for the manganese toxicity in these cases is not clear.

 

Pathology of manganese toxicity

Both these two main causes of manganese poisoning lead to a similar pathological picture, the main features of which are neurological. Recent MRI techniques have shown hyperintense areas of discharge in the basal ganglia, temporal and frontal lobes, cerebellum and centrum ovale (Alves 1997). Clinically the most obvious changes are located in the basal ganglia leading to extrapyramidal signs and a picture closely resembling that of Parkinsonís disease.

 

In both cases dopamine depletion has been found to occur in the basal ganglia and has been found to be benefited by treatment with L-Dopa (Reynolds 2002). In industrial poisoning cases, these changes appear to be irreversible. Yamada et el. (1986) for example found persistent degenerative changes in the basal ganglia 5 years after cessation of the industrial exposure. In shorter term exposure related to total parenteral nutrition reversal of the neurological picture and the associated MRI findings appears to be possible (Mirovitz 1992, Ejima 1992, Reynolds 1994).

 

Conclusions

With the decline of manganism as an industrial hazard concern over the dangers of manganese toxicity has shifted to the problems raised by prolonged cholestasis and total parenteral nutrition. These complications are still not widely appreciated amongst the medical community and the level of awareness needs to be raised amongst physicians as these complications are now susceptible to diagnosis, treatment and cure if picked up early. With advances in medical care they are likely to pose an increasing problem.

 

References

1. Reynolds AP. (2002) Lecture notes. Surrey University

2. Nielsen FH. (2001) Boron, Manganese, Molybdenum, and Other Trace Elements. In: Present Knowledge of Nutrition. 8th ed. ILSI Press, Washington, DC

3. Couper J. (1837) On the effects of black oxide of manganese when inhaled into the lung. Br Ann Med Pharmacol 1: 41-142

4. Cotzias GC, Horiuchi K, Fuenzalida S, et al. (1968) Chronic manganese poisoning. Neurology 18: 376-382

5. Yamada M, Ohno S, Okayasu I, et al. (1986) Chronic manganese poisoning. A neuropathological study with determination of manganese distribution in the brain. Acta Neuropathol 70: 273-278

6. Krieger D, Krieger S, Jansen O, et al. (1995) Manganese and chronic hepatic encephalopathy. Lancet 346: 270-274

7. Reynolds AP, Kiely E, Meadows N. (1994) Manganese in long term paediatric parenteral nutrition. Arch Dis Child 71: 527-528

8. Mirovitz SA, Westrich TJ. (1992) Basal ganglia signal intensity alterations: Reversal after discontinuation of parenteral manganese administration. Radiology 185: 535-536

9. Alves G, et al. (1997) Neurological disorders due to brain manganese deposition in a jaundiced patient receiving long-term parenteral nutrition. J Parent & Enteral Nutr 21(1): 41-45

10. Ejima A, Imamura T, Nakamura S, et al. (1992) Manganese intoxication during total parenteral nutrition. Lancet 339: 426