OVERVIEW

What is copper deficiency myeloneuropathy?

The proper functioning of the human nervous system relies on certain key enzymes, and copper is an essential component of these enzymes.

Copper deficiency myeloneuropathy is a neurodegenerative disorder caused by copper deficiency. Patients may experience sensory ataxia, spastic paralysis, and peripheral nerve damage, often accompanied by hematological abnormalities such as anemia and leukopenia, which are typical manifestations.

After diagnosis, long-term oral copper supplementation is usually required, including copper acetate, copper sulfate, copper citrate, or copper gluconate, with a dosage of 2–8 mg/d of elemental copper.

Following copper therapy, hematological symptoms generally improve or fully recover. However, neurological symptoms may stabilize, improve, or even worsen. In summary, early diagnosis and treatment are crucial when patients exhibit unsteady gait, sensory abnormalities, or anemia.

Is copper deficiency myeloneuropathy common?

Most patients with copper deficiency myeloneuropathy are adults over 30 years old, and it is more prevalent in women than in men. Due to limited research, the exact incidence remains unknown.

Is copper deficiency myeloneuropathy the same as Menkes kinky hair syndrome?

No.

Although both conditions are caused by copper deficiency, Menkes kinky hair syndrome is a genetic disorder with poor treatment response even with copper supplementation. In contrast, copper deficiency myeloneuropathy can be alleviated with copper therapy.

SYMPTOMS

What are the common manifestations of copper deficiency myeloneuropathy?

Copper deficiency myeloneuropathy often involves the spinal cord, peripheral nerves, and hematopoietic system.

• Neurological manifestations:

  • Myelopathy typically presents as spastic gait instability, marked sensory ataxia, and impaired vibration and position sense.

  • Peripheral neuropathy may manifest as sensory abnormalities in the lower limbs, with sock-like distribution of impaired pain and temperature sensation, often accompanied by hyperreflexia in the knees and hyporeflexia in the ankles.

  • Variable degrees of optic nerve involvement may occur.

• Hematological manifestations: Mainly include anemia and leukopenia.

• Others: Liver diseases such as cirrhosis.

How does copper deficiency myeloneuropathy develop?

The proper functioning of the human nervous system relies on key enzymes that require copper as an essential component. Copper deficiency impairs these enzymes, leading to neurological dysfunction.

Additionally, copper maintains hematopoietic function, and its deficiency disrupts iron metabolism, causing anemia. The disease progresses slowly, usually with a chronic or subacute onset.

What severe consequences can copper deficiency myeloneuropathy cause?

Severe copper deficiency in young children may result in delayed reactions, speech delays, and unsteady walking. In adults, the disease can lead to gait instability, spastic paraplegia of the lower limbs, and blindness.

CAUSES

What causes copper deficiency myeloneuropathy?

The exact etiology of copper deficiency myeloneuropathy is not fully understood, but known causes primarily include malabsorption of copper (commonly seen after gastric surgery) or excessive zinc intake. Possible contributing factors include:

• Patients with a history of gastric surgery—this is the most common cause. With the increasing prevalence of bariatric surgery (weight-loss surgery), copper deficiency is becoming more prominent. In most cases, neurological symptoms appear several years after gastric surgery.

• Excessive zinc intake may also lead to copper deficiency because copper and zinc compete for absorption in the gastrointestinal tract. Over-supplementation of zinc increases copper excretion, resulting in malabsorption. Zinc is often added to over-the-counter medications for treating the common cold and is also used in denture adhesives. Therefore, excessive zinc supplementation can cause copper deficiency.

• A history of malabsorption-related intestinal diseases, such as chronic diarrhea, cystic fibrosis, celiac disease, and inflammatory bowel disease, may also contribute to copper deficiency.

• Use of copper-chelating agents may lead to copper deficiency.

• Patients undergoing long-term peritoneal dialysis or hemodialysis.

• Long-term total parenteral nutrition (intravenous feeding), especially when copper is not supplemented due to cholestasis or other reasons, increases the risk of copper deficiency.

• In rare cases, preterm infants fed with formula without adequate copper supplementation may develop copper deficiency.

Is copper deficiency myeloneuropathy hereditary?

No, it is not hereditary.

This condition is acquired due to malabsorption or excessive zinc supplementation. The hereditary disorder associated with copper deficiency is Menkes kinky hair syndrome, an X-linked congenital genetic disease characterized by clinical manifestations of copper deficiency.

DIAGNOSIS

How is copper deficiency myeloneuropathy diagnosed?

When diagnosing copper deficiency myeloneuropathy, doctors primarily rely on the patient's characteristic clinical syndrome and laboratory indicators of copper deficiency (mainly serum copper and ceruloplasmin levels).

In addition to the above hematological copper tests, patients with copper deficiency myeloneuropathy should also undergo spinal imaging, such as magnetic resonance imaging (MRI), to rule out other diseases.

Furthermore, vitamin B₁₂ levels may need to be tested (especially in patients with a history of gastric surgery) to exclude a diagnosis of isolated or combined vitamin B₁₂ deficiency.

What tests are needed for copper deficiency myeloneuropathy?

Diagnosing copper deficiency myeloneuropathy requires laboratory indicators and imaging tests:

• Reduced serum copper or ceruloplasmin levels (over 90% of circulating copper is bound to ceruloplasmin), though borderline copper-deficient patients may show normal values. Ceruloplasmin, as an acute-phase reactant, may remain normal in inflammatory conditions (e.g., infections, hematologic diseases, malignancies) even with low copper stores.

• If excessive zinc intake is suspected, serum zinc and 24-hour urinary zinc excretion levels should be tested.

• For patients with a history of gastric surgery, vitamin B₁₂ levels should be checked, as vitamin B₁₂ deficiency can coexist with copper deficiency.

• Spinal imaging, typically MRI, is recommended for all myelopathy patients during initial evaluation.

• Nerve conduction studies, other electrophysiological tests, lumbar puncture, and cerebrospinal fluid analysis are not routinely performed and are decided by the doctor based on clinical assessment.

Which diseases are easily confused with copper deficiency myeloneuropathy? How to differentiate them?

• Copper deficiency myeloneuropathy is easily confused with neurological disorders caused by vitamin B₁₂ deficiency. If vitamin B₁₂ supplementation fails to halt neurological progression, further tests for copper deficiency myeloneuropathy should be conducted to confirm copper deficiency.

• Copper deficiency myeloneuropathy may be confused with Menkes kinky hair syndrome. Menkes disease is an inherited disorder presenting as copper deficiency, manifesting in early infancy with severe symptoms, including characteristic "kinky" hair, growth retardation, hypopigmentation, and skeletal abnormalities.

TREATMENT

Which department should I visit for copper deficiency myeloneuropathy?

Neurology.

Can copper deficiency myeloneuropathy heal on its own?

No, it will not heal on its own and will only worsen. Copper supplementation is required for symptom relief. If severe neurological symptoms are already present at the time of diagnosis, they may persist even after treatment.

How is copper deficiency myeloneuropathy treated?

There is currently no optimal regimen for copper supplementation in terms of dosage, duration, route, or form. However, many treatment approaches are feasible. The main treatment methods include:

• First, address predisposing factors. For example, if excessive zinc intake is suspected, discontinuing zinc supplements may suffice, or additional copper supplementation may be needed initially.

• Since long-term copper supplementation is required, oral administration is preferred, using forms such as copper acetate, copper sulfate, copper citrate, or copper gluconate, at a dose of 2–8 mg of elemental copper per day.

• Some patients may require higher doses, typically starting with 8 mg/day orally, then gradually reducing to 4–6 mg/day, and finally to 2 mg/day. Regular monitoring of serum copper levels is necessary to assess adequacy and determine the best long-term treatment strategy.

• For patients receiving copper supplements via jejunostomy tubes, absorption may be insufficient, necessitating injectable therapy. Severe copper deficiency or malabsorption may also require injectable treatment as the preferred option.

What is the prognosis for copper deficiency myeloneuropathy?

After copper supplementation, hematological manifestations (red blood cells, white blood cells, serum copper, and ceruloplasmin levels) generally improve or return to normal. Neurological symptoms may stabilize, improve, or in some cases, continue to worsen.

DIET & LIFESTYLE

What should patients with copper deficiency myeloneuropathy pay attention to in their diet?

In terms of diet, they can consume more copper-rich foods, such as vegetables, grains, legumes, liver, oysters, shellfish, and nuts.

What should patients with copper deficiency myeloneuropathy pay attention to in daily life?

In daily life, they should use zinc-containing over-the-counter medications appropriately. Zinc, as an over-the-counter dietary supplement, is included in many over-the-counter cold medicines and is also used as a denture adhesive. When using it, strictly follow the dosage and instructions on the label to avoid excessive zinc supplementation.

Does copper deficiency myeloneuropathy require follow-up examinations? How should they be conducted?

Follow-up examinations are necessary, especially during copper supplementation. Regular serum copper tests are needed to assess whether the supplementation therapy is adequate and to determine the most suitable long-term treatment strategy.

PREVENTION

Can Copper Deficiency Myeloneuropathy Be Prevented? How to Prevent It?

To some extent, copper deficiency myeloneuropathy can be prevented by addressing its causes. For example, zinc supplements should be used rationally, and patients who have undergone gastric surgery or dialysis should regularly monitor serum copper levels. Additionally, attention should be paid to dietary supplementation, with increased consumption of copper-rich foods.