Can manganese deficiency cause ataxia?

Manganese Deficiency and Ataxia: Clinical Relationship

Yes, manganese deficiency can cause ataxia, as evidenced by animal models where manganese deficiency leads to impaired skeletal development and ataxia. 1

Pathophysiological Basis

Manganese is an essential trace element that serves as a cofactor for several critical enzymes in the body, including:

• Mitochondrial superoxide dismutase
• Pyruvate carboxylase
• Arginase
• Glutamine synthetase
• Phosphoenolpyruvate decarboxylase 1

These enzymes play crucial roles in:

• Antioxidant defense
• Carbohydrate metabolism
• Proper neurological function
• Skeletal development

Evidence from Animal Models

The relationship between manganese deficiency and ataxia is well-documented in animal studies:

• In animal models, manganese deficiency affects mucopolysaccharide and liposaccharide formation 1
• This leads to impaired skeletal development and ataxia 1, 2
• A specific congenital ataxia can be caused by manganese deficiency during prenatal development in mice 3
• The ataxia results from defective development of the otoliths (inner ear structures) 3

Clinical Implications

While manganese deficiency is rare in humans due to its widespread presence in foods, certain populations may be at risk:

1. Patients on long-term parenteral nutrition (PN):

   • Manganese should be supplied at a dose of no more than 1 mg/kg/day (maximum 50 mg/day) 1
   • Regular monitoring of manganese levels is recommended 1

2. Patients with Friedreich ataxia:

   • Research suggests a link between frataxin deficiency (the cause of Friedreich ataxia) and manganese deficiency 4
   • Manganese supplementation restored activity of certain iron-sulfur enzymes in a yeast model 4

Diagnostic Considerations

When evaluating potential manganese deficiency:

• Measure whole blood or RBC manganese concentrations 1
• Consider neurological examination for signs of ataxia
• Monitor patients on long-term PN regularly 1

Therapeutic Approach

For suspected manganese deficiency:

• Enteral nutrition should provide 2-3 mg manganese per day 1
• For parenteral nutrition, provide 1 mg/kg/day (maximum 50 mg/day) 1
• Balance supplementation carefully, as manganese toxicity can also cause neurological symptoms including a Parkinson-like disease 1

Caution: Manganese Toxicity

It's important to note that while deficiency can cause ataxia, manganese toxicity is more common clinically and can cause:

• Headache, asthenia, irritability, fatigue
• Neurodegenerative syndrome with psychiatric symptoms (manganism)
• Parkinson-like motor defects 1
• Hepatic failure in cases of acute overdose 5

Toxicity is particularly concerning in patients with:

• Cholestasis
• Liver failure
• Hepatic encephalopathy
• Iron deficiency 1

Conclusion

While manganese deficiency is rare in clinical practice, it should be considered in the differential diagnosis of ataxia, particularly in patients on long-term parenteral nutrition or with conditions that might affect manganese metabolism.