What are the signs of copper deficiency?

Signs and Symptoms of Copper Deficiency

Copper deficiency presents with distinct hematological, neurological, and physical manifestations including microcytic anemia, neutropenia, myelopathy with sensory ataxia, and characteristic skin and hair changes. 1

Clinical Presentation

Hematological Manifestations

• Microcytic anemia (most common hematological finding) 1
• Neutropenia 1
• Pancytopenia in severe cases 2
• Sideroblastic anemia (can mimic myelodysplastic syndrome) 2

Neurological Manifestations

• Myelopathy with spastic gait and prominent sensory ataxia (resembling subacute combined degeneration seen in B12 deficiency) 3
• Peripheral neuropathy with decreased vibration and proprioception 4
• Paresthesia in extremities 4
• Progressive weakness in both upper and lower extremities 5
• Psychomotor retardation (particularly in infants) 6
• Hypotonia (particularly in infants) 6

Physical and Dermatological Signs

• Delayed wound healing 1
• Hair depigmentation 1
• Hypopigmentation of skin 6
• Pallor 6
• Taste alterations 1

Skeletal Manifestations (Particularly in Children)

• Osteoporosis 1
• Bone fractures (particularly in infants with severe deficiency) 6
• Radiologic changes including:
  • Cupping and fraying of metaphyses 6
  • Sickle-shaped metaphyseal spurs 6
  • Significant bone demineralization 6
  • Subperiosteal new bone formation 6

High-Risk Populations

Copper deficiency should be particularly suspected in patients with:

1. History of bariatric surgery, especially Roux-en-Y gastric bypass 1, 7
2. Gastrectomy or other gastric surgeries 5
3. Short bowel syndrome or multiple small bowel resections 5
4. Prolonged parenteral nutrition without adequate copper supplementation 1
5. High-dose zinc supplementation (which interferes with copper absorption) 1
6. Continuous renal replacement therapy 1
7. Preterm infants (who have lower copper stores) 6
8. Severe nutritional disorders (liver failure, short gut syndrome) 6

Diagnostic Considerations

• Serum copper levels <12 μmol/L with elevated CRP (>20 mg/L) suggest copper deficiency 1
• Levels <8 μmol/L (with or without elevated CRP) confirm copper deficiency 1
• Important to differentiate from other conditions with similar presentations:
  • Vitamin B12 deficiency (can coexist with copper deficiency) 3
  • Myelodysplastic syndrome 2
  • Menkes disease (X-linked recessive condition with copper metabolism defect) 6

Clinical Pitfalls and Caveats

1. Neurological manifestations may be irreversible if diagnosis and treatment are delayed, while hematological abnormalities typically resolve with supplementation 5

2. Copper deficiency can occur without anemia - neurological symptoms may be the only presenting feature 3

3. Copper deficiency is frequently underrecognized as a cause of anemia, neutropenia, and bone marrow dysplasia 2

4. In infants, copper deficiency is not likely to be observed in full-term children younger than 6 months or preterm infants younger than 2.5 months due to sufficient fetal copper stores 6

5. Copper deficiency can mimic B12 deficiency in clinical presentation and neuroimaging findings 3

6. Patients may have hyperzincemia even without exogenous zinc supplementation 3

Given the potentially irreversible neurological damage that can occur with copper deficiency, clinicians should maintain a high index of suspicion in at-risk populations, particularly those with a history of bariatric surgery or malabsorptive conditions 5, 4.