Clinical Signs of Copper Deficiency in Post-Bariatric Surgery Patients
Copper deficiency after Roux-en-Y gastric bypass presents with a characteristic triad of hematologic abnormalities (anemia, neutropenia, leukopenia), myeloneuropathy with gait disturbances and sensory ataxia, and less commonly thrombocytopenia—with neurological symptoms often being irreversible if treatment is delayed. 1, 2, 3
Hematologic Manifestations
The blood-related signs are typically the first to appear and most readily reversible:
- Anemia of variable morphology (microcytic, normocytic, or macrocytic) is the most common presentation 1, 4, 5
- Neutropenia and leukopenia occur frequently and may be severe enough to mimic myelodysplastic syndrome 1, 4, 5
- Thrombocytopenia is relatively rare but can occur 4
- Bone marrow examination may show vacuolation of myeloid and/or erythroid precursors, ring sideroblasts, iron-containing plasma cells, and decreased granulocyte precursors—findings that strongly suggest copper deficiency and should prompt immediate copper assessment 2, 5
Neurological Manifestations
These are the most concerning signs because they may become permanent if treatment is delayed:
- Myeloneuropathy presenting as spastic gait with prominent sensory ataxia, clinically indistinguishable from vitamin B12 deficiency (subacute combined degeneration) 1, 2, 3, 6
- Posterior column dysfunction with impaired proprioception and vibration sense 2, 6
- Progressive gait abnormalities and severe ataxia that may not fully resolve even with treatment 3, 7
- Upper and lower extremity weakness and paresthesias 7, 6
- Neurological symptoms may be present even without hematologic abnormalities 6
Other Clinical Signs
Additional manifestations related to copper's role as an enzymatic cofactor:
- Osteoporosis from impaired collagen synthesis via lysyl oxidase 1
- Hair depigmentation due to copper's essential role in melanin synthesis 1
- Delayed wound healing in acute deficiency 1, 8
- Cardiac arrhythmias in rare acute presentations 1
Critical Diagnostic Pitfalls
Always check vitamin B12 levels simultaneously with copper, as the neurological presentations are clinically identical and both deficiencies may coexist in post-bariatric patients 2, 6. The myeloneuropathy can be mistaken for multiple sclerosis or other demyelinating diseases if copper deficiency is not considered 3, 6.
Check both zinc AND copper levels together before initiating any treatment, as zinc excess is a common cause of copper deficiency through competitive intestinal absorption, and high-dose zinc supplementation (>30 mg daily) can precipitate or worsen copper deficiency 2, 9, 8.
Measure C-reactive protein (CRP) alongside copper levels to differentiate true copper deficiency from inflammatory conditions that falsely elevate ceruloplasmin (the copper-carrying protein) 2. With plasma copper <12 μmol/L and CRP >20 mg/L, deficiency is likely; with values <8 μmol/L regardless of CRP, repletion is mandatory 1, 2.
Timeline and Monitoring
- Symptoms require several weeks to develop after copper depletion begins and are not readily recognized initially 1
- Post-Roux-en-Y gastric bypass patients require copper level monitoring every 6-12 months indefinitely due to their high-risk status 2, 8
- Hematologic abnormalities respond promptly to copper replacement (often within days), but neurological deficits show only partial or no improvement even with aggressive treatment 3, 7, 4