Copper deficiency neuropathy (CDAP) is a specific form of nerve damage caused by insufficient levels of the trace mineral copper. Copper is fundamental for numerous biological systems, including the central and peripheral nervous systems. When copper levels drop too low, the resulting dysfunction leads to progressive and often debilitating neurological symptoms. Recognizing this condition is important because its symptoms frequently mimic those of other common disorders, potentially delaying necessary treatment.
Essential Functions of Copper and Causes of Deficiency
Copper serves as a cofactor for metalloenzymes that carry out biological processes. In the nervous system, it is necessary for maintaining the integrity of the myelin sheath, the fatty layer that insulates nerve fibers and allows for rapid signal transmission. Copper’s involvement in myelination is partly due to its role as a cofactor for cytochrome c oxidase, an enzyme required for cellular energy production.
Copper is also a component of copper/zinc-superoxide dismutase, an antioxidant enzyme that protects cells from damaging free radicals. When copper is deficient, enzyme activity is compromised, leading to increased oxidative stress and impaired energy metabolism within nerve cells. This failure underlies the subsequent nerve damage.
Acquired copper deficiency is most frequently a consequence of impaired absorption rather than inadequate dietary intake alone. A common cause is upper gastrointestinal surgery, such as bariatric procedures like gastric bypass, which reduce the area available for copper absorption. Other malabsorption syndromes, including celiac disease or inflammatory bowel disease, can also interfere with copper uptake.
Another significant cause is excessive intake of zinc, typically through high-dose supplements or denture creams containing zinc. Zinc competes with copper for absorption by inducing the production of metallothionein. Metallothionein binds copper with high affinity, trapping it within intestinal cells, which are then shed and excreted, effectively blocking copper from entering the bloodstream.
Identifying the Neurological Symptoms
Copper deficiency neuropathy typically involves two distinct forms of nerve damage: peripheral neuropathy and myelopathy. Peripheral neuropathy manifests as numbness, tingling sensations (paresthesia), and loss of sensation, often beginning in the hands and feet in a “glove-and-stocking” pattern. This sensory loss is due to damage to the long sensory nerves, resulting in a distal axonal sensorimotor neuropathy.
Myelopathy refers to dysfunction of the spinal cord, specifically affecting the dorsal columns that carry information about vibration and position sense. Damage to these columns is the primary cause of sensory ataxia, characterized by gait instability, poor balance, and unsteadiness while walking. Patients often describe difficulty coordinating movements, particularly in low light or when their eyes are closed, as they rely on vision to compensate for the lost sense of position.
These neurological symptoms may closely resemble subacute combined degeneration, a condition associated with severe vitamin B12 deficiency. The myelopathy can also be accompanied by spasticity and hyperactive reflexes, further complicating the clinical picture. In addition to the neurological issues, many patients with copper deficiency also exhibit hematological abnormalities, most commonly anemia and neutropenia, though nerve damage can occur even without these blood changes.
Diagnosis and Management
Diagnosing copper deficiency neuropathy requires clinical evaluation, laboratory testing, and sometimes imaging studies to rule out other conditions. Initial laboratory tests measure the levels of copper and its primary transport protein, ceruloplasmin, in the blood. In acquired copper deficiency, both serum copper and serum ceruloplasmin levels are typically low. Testing 24-hour urinary copper excretion is also performed; this is usually low or normal, helping distinguish copper deficiency from copper overload diseases like Wilson’s disease. Nerve conduction studies may confirm an axonal, sensorimotor peripheral neuropathy, while MRI of the spine might show characteristic signal changes in the posterior columns.
Treatment focuses on two primary goals: correcting the copper deficit and addressing the underlying cause of malabsorption. Copper repletion is usually achieved through oral supplementation, often starting with higher doses (e.g., 2 to 8 milligrams per day) before tapering to a maintenance dose. For patients with severe neurological symptoms or significant malabsorption, intravenous copper administration may be necessary to bypass the gut and rapidly restore systemic levels. It is essential to identify and eliminate the source of the deficiency, such as discontinuing high-dose zinc supplements or managing the underlying gastrointestinal disorder.
Hematological parameters, such as anemia, often normalize quickly, typically within a few weeks of starting treatment. However, neurological recovery is much slower and less predictable; while further progression of the neuropathy may cease, existing nerve damage often reverses only partially. Therefore, early diagnosis and prompt treatment are necessary to maximize the potential for neurological improvement and prevent permanent disability.