What Are the Major Diseases Involving Copper Metabolism?

Patient Presentation
A 2-year-old male was admitted after a planned gastric tube placement because of recurrent pneumonias and difficulty handling his secretions. He did well during and after the surgery but because of previous anesthesia problems he was monitored overnight. The past medical history showed that he was premature with hypoxic ischemic encephalopathy, developmental delay and seizures. He also had a not-fully defined copper metabolism problem.

The pertinent physical exam showed a non-verbal child who responded to his parents and caretakers with a smile and some purposeful movements. The gastric tube was in place without bleeding. Neurological examination showed hypertonia with stiff heel cords. The diagnosis of a child with multiple medical problems, status-post gastric tube placement was made. The residents commented that they didn’t know much about copper problems other than they occurred with Menke’s kinky hair disease and Wilson’s disease. The staff pediatrician also agreed and they decided to look up more information and report back to the team the following day.

Nutritional problems can occur in all parts of the world and in all socioeconomic strata. Caloric and/or protein inadequacy unfortunately plagues too many people because of inadequate supplies or availability. Supplemental food programs around the world attempt to provide appropriate nutrition, but can be stymied because of war, political instability, economic instability and many other social factors.

The most common specific nutrient deficiencies are iron and Vitamin D deficiencies. Minerals important for essential nutrition include copper, iodine, selenium and zinc. A typical mixed diet usually provides enough minerals. In the United States, mineral deficiencies are usually uncommon unless there is an underlying disease process or abnormal food restrictions or diet. Vegan and other vegetarian diets can provide enough minerals but certain foods may need to be increased to ensure adequate intake.

Copper is a cofactor in many enzymes include ceruloplasmin, cytochrome oxidase, superoxide dismutase, elastase, lysyl oxidase, dopamine-β-hyroxylase, tyrosinase, and ascorbic acid oxidase. With too much copper, there is the potential to induce reactive free radicals and cause cellular damage. Abnormalities of copper metabolism are caused by genetic mutations in copper-transporting ATPases.

Copper is available in many foods including liver, shellfish, sunflower seeds, nuts, lentils and even chocolate. It is a component of breast milk (0.2 -0.4 mg/L) in small amounts but is very bioavailable. The World Health Organizations recommends 60 micrograms/kg/day for infants and up to 900 micrograms/day for adults. Increased amounts of copper are needed during growth phases, so it is not surprising that copper deficiency is associated with poor growth patterns or diseases that also cause growth problems. Preterm infants generally have low copper levels for the first 4-6 months of life.

Copper is absorbed from the intestine into the blood and transported to the liver where is excreted in bile; a small amount is excreted in urine. Copper is processed mainly in the Golgi apparatus and cytoplasm of the hepatocytes.

Learning Point
Copper abnormalities occur in:

  • Menke’s kinky hair disease – an X-linked recessive disorder seen in 1/150,000 male births caused by the ATP7A gene which causes a copper deficiency. Problems include aberrant hair, connective tissue disorders, hypothermia, growth abnormalities, and cerebral and cerebellar degeneration including seizures, hypotonia, and developmental delay. Effects manifest usually between 2-4 months, and most children die by age 3 years. Treatment is copper-histadine injections.
  • Occipital horn syndrome – an X-linked recessive very rare syndrome caused by the ATP7A gene which causes a copper deficiency. Patients have connective tissue disorders and ataxia. Problems are similar to Menke’s kinky hair disease. No treatment is readily available.
  • Wilson’s disease – an autosomal recessive disorder seen in 1/30,000-50,000 live births caused by the ATP7B gene which causes copper excess and cellular toxicity. It causes hepatic disease, neurological and psychiatric abnormalities (dysarthria, dystonia, chorea/athetosis, and seizures), arthritis, cardiomyopathy, hematuria, Kayser-Fleischer rings, and pancreatitis. Treatment includes chelating agents and zinc.

Copper abnormalities also can occur secondarily to patients dependent on total parental nutrition, short bowel syndrome and in burn patients. It can also be associated with problems gaining weight, hypochromic anemia during iron supplementation, neutropenia, and osteoporsis.

Questions for Further Discussion
1. What are Kayser Fleischer rings?
2. What diseases are caused by zinc abnormalities?
3. What diseases are caused by iodine abnormalities?
4. What diseases are caused by selenium abnormalities?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Minerals and Wilson’s Disease.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Higdon J, Drake VJ, Turlund JR. Linus Pauling Institute
Micronutrient Research for Optimum Health. Copper.
Available from the Internet at http://lpi.oregonstate.edu/infocenter/minerals/copper/ (rev. 2007, cited 11/21/11).

Suskind DL. Nutritional deficiencies during normal growth.
Pediatr Clin North Am. 2009 Oct;56(5):1035-53.

Shah MD, Shah SR. Nutrient deficiencies in the premature infant.
Pediatr Clin North Am. 2009 Oct;56(5):1069-83.

Kodama H, Fujisawa C, Bhadhprasit W.
Pathology, clinical features and treatments of congenital copper metabolic disorders–focus on neurologic aspects.
Brain Dev. 2011 Mar;33(3):243-51.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.
    16. Learning of students and other health care professionals is facilitated.


    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital