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by Larry E. Johnson, MD, PhD

Copper is a component of many body proteins; almost all of the body’s copper is bound to copper proteins. Unbound (free) copper ions are toxic. Genetic mechanisms control the incorporation of copper into apoproteins and the processes that prevent toxic accumulation of copper in the body. Copper absorbed in excess of metabolic requirements is excreted through bile.

Acquired Copper Deficiency

If the genetic mechanisms controlling copper metabolism are normal, dietary deficiency rarely causes clinically significant copper deficiency. Causes include

  • Severe childhood protein deficiency

  • Persistent infantile diarrhea (usually associated with a diet limited to milk)

  • Severe malabsorption (as in sprue or cystic fibrosis)

  • Gastric surgery (where vitamin B12 deficiency may also be present)

  • Excessive zinc intake

Deficiency may cause neutropenia, impaired bone calcification, myelopathy, neuropathy, and hypochromic anemia not responsive to iron supplements.

Diagnosis is based on low serum levels of copper and ceruloplasmin, although these tests are not always reliable.

Treatment is directed at the cause, and copper 1.5 to 3 mg/day po (usually as copper sulfate) is given.

Inherited Copper Deficiency

(Menkes Syndrome)

Inherited copper deficiency occurs in male infants who inherit a mutant X-linked gene. Incidence is about 1 in 100,000 to 250,000 live births. Copper is deficient in the liver, serum, and essential copper proteins, including cytochrome-c oxidase, ceruloplasmin, and lysyl oxidase.

Symptoms and Signs

Symptoms of inherited copper deficiency are severe intellectual disability, vomiting, diarrhea, protein-losing enteropathy, hypopigmentation, bone changes, and arterial rupture; the hair is sparse, steely, or kinky.

Most affected children die by age 10 yr.


  • Serum copper and ceruloplasmin levels

Diagnosis of inherited copper deficiency is based on low copper and ceruloplasmin levels in serum. Because early diagnosis and treatment seem to result in a better prognosis, the disorder is ideally detected before age 2 wk. However, diagnostic accuracy of these tests is limited. Thus, other tests are being developed.


  • Copper histidine

Parenteral copper is usually given as copper histidine 250 mcg sc bid to age 1 yr, then 250 mcg sc once/day until age 3 yr; monitoring of kidney function is essential during treatment.

Despite early treatment, many children have abnormal neurodevelopment.

Acquired Copper Toxicity

Acquired copper toxicity can result from ingesting or absorbing excess copper (eg, from ingesting an acidic food or beverage that has had prolonged contact with a copper container). Self-limited gastroenteritis with nausea, vomiting, and diarrhea may occur.

More severe toxicity results from ingestion (usually with suicidal intent) of gram quantities of a copper salt (eg, copper sulfate) or from absorption of large amounts through the skin (eg, if compresses saturated with a solution of a copper salt are applied to large areas of burned skin). Hemolytic anemia and anuria can result and may be fatal.

Indian childhood cirrhosis, non-Indian childhood cirrhosis, and idiopathic copper toxicity are probably identical disorders in which excess copper causes cirrhosis. All appear to be caused by ingesting milk that has been boiled or stored in corroded copper or brass vessels. Studies suggest that idiopathic copper toxicity may develop only in infants with an unknown genetic defect.

Diagnosis usually requires liver biopsy, which may show Mallory hyalin bodies.

Treatment of Acquired Copper Toxicity

  • Chelation

  • Supportive measures

For copper toxicity due to ingesting grams of copper, prompt gastric lavage is done. Copper toxicity that causes complications such as hemolytic anemia, anuria, or hepatotoxicity is also treated with either oral penicillamine 250 mg q 6 h to 750 mg q 12 h (1000 to 1500 mg/day in 2 to 4 doses) or dimercaprol 3 to 5 mg/kg IM q 4 h for 2 days, then q 4 to 6 h ( chelation therapy).

If used early, hemodialysis may be effective.

Occasionally, copper toxicity is fatal despite treatment.

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