What are the signs and symptoms of copper deficiency?

Signs and Symptoms of Copper Deficiency

Copper deficiency presents with distinct hematologic, neurologic, and other systemic manifestations that can lead to significant morbidity and mortality if left untreated, particularly as neurological damage may be irreversible.

Clinical Manifestations

Hematologic Manifestations

• Microcytic anemia (can also be macrocytic)
• Neutropenia
• Pancytopenia in severe cases 1, 2
• Sideroblastic anemia 2
• Myelodysplasia-like picture (can mimic myelodysplastic syndrome) 1

Neurologic Manifestations

• Myeloneuropathy (similar to subacute combined degeneration seen in B12 deficiency) 3
• Peripheral neuropathy with sensory and motor disturbances 1
• Ataxia and gait abnormalities 1, 3
• Paresthesias in extremities 3
• Decreased vibration and proprioception 3

Other Systemic Manifestations

• Osteoporosis 4, 1
• Hair depigmentation (copper is essential for melanin synthesis) 4, 1
• Delayed wound healing 4, 1
• Fatigue 1, 5
• Impaired immune function 1
• Cardiac arrhythmias (in acute deficiency) 4

High-Risk Populations

Copper deficiency is particularly common in:

• Patients after bariatric surgery, especially gastric bypass 1, 6, 7
• Patients with malabsorptive conditions including Crohn's disease 1, 5
• History of gastrectomy or small bowel resections 1, 5
• Patients on prolonged parenteral nutrition without adequate copper 4, 1
• Patients undergoing continuous renal replacement therapy 4, 1
• Preterm infants (lower copper stores than term infants) 4
• Children with severe nutritional disorders (liver failure, short gut syndrome) 4

Diagnostic Approach

Laboratory Testing

• Serum copper levels:
  • <12 μmol/L with elevated CRP >20 mg/L suggests deficiency
  • <8 μmol/L regardless of CRP confirms deficiency 4, 1
• Complete blood count to assess for anemia and neutropenia 1
• Ceruloplasmin levels (often low in copper deficiency) 1
• Always check zinc levels simultaneously (high zinc can cause copper deficiency) 1

Radiologic Findings in Children

• Cupping and fraying of the metaphyses
• Sickle-shaped metaphyseal spurs
• Significant demineralization
• Subperiosteal new bone formation 4

Treatment

Supplementation Guidelines

• For mild to moderate deficiency: oral supplementation with 4-8 mg/day of elemental copper 4, 1
• For severe deficiency: intravenous copper supplementation may be required 5, 6
• Maintain a ratio of 8-15 mg zinc to 1 mg copper when supplementing both minerals 1

Monitoring

• Recheck copper levels after 3 months of supplementation 1
• Monitor for improvement in hematological parameters 1
• Be aware that while hematological abnormalities often correct with supplementation, neurological manifestations may be irreversible if diagnosis and treatment are delayed 1, 5, 6

Important Clinical Considerations

• Copper deficiency can mimic vitamin B12 deficiency or myelodysplastic syndrome, leading to misdiagnosis 1, 2
• Symptoms typically take weeks to develop and may not be readily recognized 4
• Early diagnosis and treatment are crucial to prevent irreversible neurological damage 1, 5
• In patients with risk factors, consider regular monitoring every 6-12 months 1
• Do not confuse acquired copper deficiency with Menkes disease, a genetic disorder of copper metabolism that occurs only in boys 4

Prompt recognition of these signs and symptoms in high-risk individuals is essential for timely intervention and prevention of permanent neurological damage.