Manganese toxicity

Background

• An essential element in the diet
  • Used in various enzymatic processes
  • Mn²⁺ can take the place of Mg²⁺, Ca²⁺, and Fe²⁺ in various proteins and enzymes, and has been seen to replace Fe²⁺ in Hgb
  • Low enteral absorption
  • Cleared by the liver and excreted in the bile
• Typical routes of exposure
  • Inhalation of dusts/fumes
    • Seen in industrial areas as manganese is used to make steel
  • Parenteral nutrition (TPN)
  • IV Methcathinone
• Readily crosses the blood brain barrier and can be seen concentrated in the basal ganglia, particularly the globus pallidus

Clinical Features

• Toxicity typically presents as cognitive issues
• Neuropsychiatric
  • Acute
    • “Manganese madness”
    • Visual hallucinations
    • Behavioral changes
    • Anxiety
    • Impotence
  • Late manifestations
    • Tremor
    • Impaired speech
    • Loss of facial expressions
    • Gait disturbances
    • Low volume speech
    • Can mimic Parkinson's disease
• Pulmonary
  • Acute / Metal fume fever
    • Fever
    • Nausea
    • Headache
    • Myalgia
    • Arthralgia
  • Chronic
    • Persistent dry cough
    • Bronchitis
    • Chemical pneumonitis
• GI
  • Anorexia
• Musculoskeletal
  • Arthralgia
  • Muscle rigidity
• Constitutional
  • Lethargy
  • Asthenia

Background

Heavy metal toxicity results from exposure to metals like lead, mercury, arsenic, or cadmium, which interfere with cellular function. Exposure may occur occupationally, environmentally, through ingestion, or from alternative medicines. Chronic toxicity can present insidiously, while acute toxicity may mimic sepsis or encephalopathy. Diagnosis is often delayed due to nonspecific symptoms.

Clinical Features

Symptoms depend on the metal and exposure duration but may include:

Neurologic: Peripheral neuropathy, confusion, tremor, encephalopathy

GI: Abdominal pain, nausea, vomiting, diarrhea, anorexia

Heme: Anemia (especially microcytic or hemolytic), basophilic stippling (lead)

Renal: Tubular dysfunction, proteinuria, Fanconi syndrome

Dermatologic: Mees’ lines (arsenic), hyperpigmentation, hair loss

Others: Fatigue, weight loss, hypertension (cadmium), immunosuppression

Differential Diagnosis

Sepsis or systemic inflammatory response

Drug toxicity or overdose

Metabolic disorders (e.g., porphyria, uremia)

Psychiatric illness (if symptoms are vague or bizarre)

Neurologic diseases (e.g., Guillain-Barré, MS, Parkinson’s)

Vitamin deficiencies (e.g., B12, thiamine)

Evaluation

Workup

History: Occupational exposures, home remedies, hobbies (e.g., jewelry making, battery recycling), diet, water source, imported goods

Labs:

• CBC, CMP, urinalysis
• Blood lead level, serum/urine arsenic, mercury, or cadmium (based on suspicion)
• Urine heavy metal screen (note: spot testing may require creatinine correction)

Imaging: Abdominal X-ray (radiopaque material in GI tract, especially with lead)

EKG: Evaluate for QT prolongation or arrhythmias in severe cases

Diagnosis

Confirmed by elevated blood or urine levels of the specific metal in the context of clinical findings. Hair and nail testing are unreliable for acute toxicity. Interpret results with toxicologist input if possible.

Management

Remove the source of exposure (e.g., occupational control, GI decontamination if recent ingestion)

Supportive care: IV fluids, seizure control, electrolyte repletion

Chelation therapy (in consultation with toxicology or Poison Control):

Lead: EDTA, dimercaprol (BAL), succimer

Mercury/arsenic: Dimercaprol or DMSA

Cadmium: No effective chelation—focus on supportive care

Notify local public health authorities if exposure source is environmental or occupational

Disposition

Admit if symptomatic, unstable, or requiring chelation

Discharge may be appropriate for asymptomatic patients with low-level exposure and outpatient follow-up

Arrange toxicology or environmental medicine follow-up for source control and serial testing

See Also

• Aluminum toxicity
• Antimony toxicity
• Arsenic toxicity
• Barium toxicity
• Bismuth toxicity
• Cadmium toxicity
• Chromium toxicity
• Cobalt toxicity
• Copper toxicity
• Gold toxicity
• Iron toxicity
• Lead toxicity
• Lithium toxicity
• Manganese toxicity
• Mercury toxicity
• Nickel toxicity
• Phosphorus toxicity
• Platinum toxicity
• Selenium toxicity
• Silver toxicity
• Thallium toxicity
• Tin toxicity
• Zinc toxicity

Evaluation

• Lab
  • Whole blood 4-15 μg/L (73-273 nmol/L)
  • Serum 0.9-2.9 μg/L (16-52 nmol/L)
  • Urine (24h) <10 μg/L (182 nmol/L)
  • No definite toxic level
  • Elevated levels are typically seen in acute toxicity, as manganese is quickly cleared from the blood
• MRI
  • Will show abnormal T1- weighted signal hyperintensity in the basal ganglia, particularly in the globus pallidus, with normal T2-weighted images

Management

• Supportive care
• Remove source of exposure
• Chelation therapy with CaNa₂EDTA or DTPA
  • Can improve urinary excretion of manganese without affecting the neurologic manifestations

Disposition

• Will depend on severity, most cases are likely seen in patients receiving TPN, and will likely need changes to their TPN orders and a consultation from nutrition
• Consult Toxicology or poison control

See Also

• Toxicology (main)
• Heavy metals

References

Soghoian, S. Manganese. In: Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill; 2011: 1294-1298