What is the differential diagnosis for a patient presenting with dizziness, headaches, and a metallic (copper) taste in the mouth?

Differential Diagnosis for Dizziness, Headaches, and Metallic (Copper) Taste

The combination of dizziness, headaches, and a metallic copper taste in the mouth should immediately raise suspicion for copper toxicity, particularly Wilson's disease in younger patients or acquired copper poisoning from environmental/dietary sources. This triad warrants urgent evaluation with serum ceruloplasmin, 24-hour urinary copper excretion, and slit-lamp examination for Kayser-Fleischer rings 1.

Primary Diagnostic Considerations

Wilson's Disease (Hepatolenticular Degeneration)

Wilson's disease must be ruled out first in any patient under 40 years presenting with neurological symptoms and should be considered even in older patients with atypical presentations 1.

Key diagnostic features:

• Serum ceruloplasmin <50 mg/L (<5 mg/dL) provides strong evidence for Wilson's disease, though 5-10% of patients may have normal levels 1
• 24-hour urinary copper excretion typically >100 μg/day (normal <40 μg/day) 1
• Kayser-Fleischer rings (golden-brown corneal deposits) are present in nearly all patients with neurological manifestations 1, 2
• Neurological symptoms include tremor, dystonia, dysarthria, and psychiatric disturbances, often accompanied by headaches and dizziness 1
• Hepatic dysfunction may be subtle or absent in patients presenting primarily with neurological symptoms 1

Critical pitfall: Normal ceruloplasmin does NOT exclude Wilson's disease—approximately 5-10% of confirmed cases have ceruloplasmin in the normal range 1. Calculate non-ceruloplasmin bound copper (serum copper minus 3× ceruloplasmin concentration) if suspicion remains high 1.

Acquired Copper Toxicity

Acute or chronic copper poisoning presents with the same symptom triad and can occur from contaminated water, dietary supplements, or occupational exposure 1, 3.

Distinguishing features:

• History of exposure to copper-containing pesticides, contaminated water (>0.1 mg/L copper), or excessive supplementation 2, 3
• Acute toxicity: hematemesis, hypotension, melena, hemolytic anemia, behavioral changes, fever, diarrhea, and abdominal cramps 1
• Chronic toxicity: malaise, weakness, abdominal pain, headache, dizziness, chest tightness, anemia (Hb 8.7-9.5 g/dL) 3
• Elevated serum copper levels (unlike Wilson's disease where total copper is often low) 1

Copper Deficiency

While less likely to cause metallic taste, copper deficiency can present with neurological symptoms and dizziness 1, 4.

Key features:

• Plasma copper <8 μmol/L indicates deficiency requiring repletion 1
• Myeloneuropathy, microcytic anemia, neutropenia, cardiac arrhythmias 1, 4
• Risk factors: post-bariatric surgery, prolonged parenteral nutrition, continuous renal replacement therapy, malabsorption 1, 4

Secondary Differential Considerations

Migraine-Associated Dizziness

Migraine frequently presents with both headache and dizziness, and these symptoms independently worsen disability 5.

• Dizziness occurs in 51.1% of headache patients, particularly with migraine 5
• Visual symptoms (52.4%) often accompany migraine episodes 5
• Metallic taste is NOT a typical migraine feature—its presence should redirect focus to copper-related disorders 6

Vestibular Disorders

True vertigo (spinning sensation) differs from light-headedness and suggests peripheral or central vestibular pathology 7, 8.

• BPPV, vestibular neuritis, Ménière's disease cause rotational vertigo with nausea/vomiting 7
• Central causes (stroke) may present with vertigo, headache, and nystagmus but not metallic taste 8
• Perform HINTS examination (Head Impulse, Nystagmus, Test of Skew) if stroke suspected 8

Cardiovascular/Orthostatic Causes

Light-headedness from presyncope presents differently than the symptom complex described 7.

• Associated with orthostatic changes, palpitations, visual graying, weakness 7
• Does NOT explain metallic taste or persistent headaches 7

Diagnostic Algorithm

Step 1: Immediate laboratory evaluation

• Serum ceruloplasmin (send to specialized lab using nephelometry or immunoassay) 1
• Serum copper and calculate non-ceruloplasmin bound copper 1
• 24-hour urinary copper excretion 1
• Complete blood count (check for anemia, neutropenia) 1, 3
• Comprehensive metabolic panel (liver function tests) 1

Step 2: Ophthalmologic examination

• Slit-lamp examination for Kayser-Fleischer rings by experienced ophthalmologist 1, 2

Step 3: Risk stratification

• Age <40 years with neurological symptoms: Wilson's disease until proven otherwise 1
• Exposure history to copper sources: consider acquired toxicity 3
• Post-bariatric surgery or malabsorption: consider copper deficiency 1

Step 4: Advanced testing if initial workup equivocal

• Liver biopsy for quantitative copper (>250 μg/g dry weight diagnostic for Wilson's) 2
• Genetic testing for ATP7B mutations 1
• Brain MRI if central neurological cause suspected 8

Critical Management Points

If Wilson's disease confirmed or highly suspected:

• Initiate chelation therapy with D-penicillamine 250-500 mg/day, titrating to 1000-1500 mg/day 1, 2
• Alternative: trientine 750-1500 mg/day if penicillamine not tolerated 1
• Dietary copper restriction to <1-2 mg/day (avoid chocolate, nuts, shellfish, mushrooms, liver) 2
• Warning: Neurological symptoms may initially worsen with penicillamine—do NOT discontinue therapy 2

If acute copper toxicity:

• D-penicillamine 250-500 mg/day for chelation 1
• Supportive care for hemolysis, renal failure 3
• Remove exposure source 3

If copper deficiency:

• Oral copper supplementation 4-8 mg/day for repletion 1
• IV copper for severe deficiency with neurological complications 4

Common Pitfalls to Avoid

• Do not dismiss metallic taste as insignificant—this symptom specifically suggests copper dysregulation and is not explained by common causes of dizziness/headache 1, 3
• Do not rely solely on ceruloplasmin—5-10% of Wilson's disease patients have normal levels 1
• Do not delay ophthalmologic examination—Kayser-Fleischer rings are pathognomonic when present with neurological symptoms 1, 2
• Do not assume age >40 excludes Wilson's disease—late presentations occur 1
• Do not confuse vestibular vertigo with this presentation—the metallic taste is the distinguishing feature pointing toward copper-related pathology 7, 8