How is Elemental Iron and Lead Related to Heme Synthesis?

Patient Presentation
A 14 month old female came to a specialty clinic for a second opinion requested by her mother about anemia and positive lead tests.
At the 12 month health maintenance visit she was found to have a hematocrit of 30% and a lead level of 21 mcg/dL (normal <10).
The patient could not be found and followed-up with until 2 months later, when the patient was retested and found to have a hemoglobin = 12.3 mg/dL, total iron = 35 mcg/dL (normal = 40-100), ferritin = 17 ng/mL (normal = 7-142), total iron binding capacity = 421mcg/dL, (normal = 225-450), iron saturation = 8% (normal = 20-50%) and lead level = 24 mcg/dL.
A wrist radiograph and abdominal radiograph showed no paint chips or lead lines. The patient was placed on treatment doses of oral iron and the health department was contacted to evaluate her home. The parents had an altercation with the health department and so the evaluation was not completed.
The past medical history revealed a full-term infant with normal developmental milestones to date.
Her home was built in the 1920s and her mother stated that it is painted with non-leaded paint currently and that it is in good repair with no peeling paint. The mother stated that she plays often on a painted porch and eats dirt from around the house’s foundation.
She does not go to daycare or spend significant time at other homes. The mother assumed that there is lead piping in the home, but there was no occupational or recreational exposure to lead by family members.
They also have not used any unglazed ceramics or eaten candy or medicines from other countries.
Mother continued to exclusively breastfeed the patient but also offers solid foods including some red meat and chicken but states that she doesn’t eat much of it. The patient did receive rice and oatmeal cereal as an infant for an uncertain amount of time. No vitamins have been given.
The review of systems showed no vomiting, diarrhea, constipation, changes in mental status or development.
The pertinent physical exam showed a developmentally appropriate toddler with growth parameters in the 10-25%. HEENT showed her to be atraumatic and normocephalic. Abdomen was soft, non-tender with no masses and normal bowel sounds. The rest of the examination was normal.
The diagnosis of iron deficiency anemia and lead poisoning were confirmed.
The laboratory evaluation was deferred as the patient had only been on the iron for a few days. The mother was counseled to offer red meat and other iron rich foods first and then if she wanted to continue the breastfeeding for emotional support to offer this afterwards. She was also instructed to give the iron with an acidic fluid such as orange juice (<4 ounces) and that introduction of a cup with whole cow’s milk would be advised.
The cow’s milk would also provide an excellent protein and calcium source in her diet.
The mother was extensively re-counseled about the need to identify the lead source which was most likely the dirt around the foundation and/or dust/paint in the home. Handouts from the health department were given and the mother agreed to implementing the dietary changes and allowing the health department to come to her home.
The patient will be re-assessed in 3-4 weeks.


Iron deficiency anemia is a hypochromic, microcytic anemia and is the most common cause of anemia in children in the United States, especially in infants and toddlers. It is defined as a hemoglobin level more than 2 standard deviations below the mean reference value for age. It is commonly caused by inadequate stores (e.g. premature infants), inadequate intake (e.g. poor nutrition) or blood loss (e.g. menses). The fetus increases its total iron body stores mainly in the last trimester of pregnancy and if the fetus is born prematurely, it does not have the opportunity to build up its iron stores.
Fetal iron stores last approximately 6 months, therefore dietary iron intake after birth is very important. Breastmilk contains iron that is bioavailable to infants, but after 6 months breastmilk does not supply enough total iron overall. Formula contains more total iron but this iron is only ~10% bioavailable to the infant. Iron containing cereals are often introduced into the infants diet at ~6 months of age for this reason.
Infants with poor nutrition often may not receive enough total iron. High milk intake may also cause a microscopic blood loss in the gastrointestinal tract, thereby exacerbating the problem.

Anemia screening is recommended at age 9-12 months, and for adolescent males and females during routine health examinations. As iron deficiency is the most common cause of anemias, often an empiric trial of therapeutic iron (2-6 mg/kg/day of elemental iron) is often started and then a complete blood count and reticulocyte count is rechecked ~ 1 month later.
If iron deficiency is the cause, then there should be an increase in hemoglobin 1-2 g/dL. Reticulocytosis can be seen as early as 3 days and peaks at 7-10 days. If appropriate increases are not seen then other causes must be sought. Parental education and possible enrollment in food supplement programs such a WIC (i.e. Women, Infants and Children) program or food stamps may help families dealing with food shortage, although families of all socioeconomic backgrounds can have iron deficiency anemia.

Other markers of iron deficiency anemia include iron stores (absent), transferrin saturation (&lt;16%), free erythrocyte protoporphyrin (>35 ng/dL), hemoglobin (&lt;11 g/dL) and mean corpuscular volume (<70 fL)

Lead poisoning is caused most often by environmental lead exposure as it is a ubiquitous heavy metal in the earth’s surface. It can permanently affect intelligence, hearing, growth and is associated with increased developmental deficits, learning disorders and possibly behavioral disorders. Studies have estimated that the intelligence quotient will drop 1-3 points for every 10 mcg/dL of blood lead level.
Children at highest risk are infants and toddlers because they are close to the ground where contaminated dirt and dust occurs and because they have frequent mouthing behaviors. Children also have a higher absorbency of lead from the gastrointestinal tract than adults (40 vs 10%).

The local health department can be helpful in identifying the cause of the lead exposure. Lead poisoning is often asymptomatic.
Common places that children are exposed include:

  • Lead based paint – from older housing especially before 1978 in the United States. Paint chips or dust are ingested. This can be increased during renovation or remodeling.
    Lead paint has a slightly sweet taste and children often like to eat the chips. It is important to remember that children often are in other environments such as a daycare center, relatives’ or friends’ homes which may also have lead. Lead abatement may actually raise lead levels. Families are often counseled to repaint the house with a non-lead based paint and to keep it in good repair.
    Additionally, frequent vacuuming to clean up dust and/or frequent washing/wiping of surfaces with a non-phosphate containing detergent can help decrease dust exposure.

  • Contaminated dirt – often found near older housing or near highways. Lead based paint may have been removed or painted over, however the dirt near the house has a high lead concentration. Lead based gasoline was previously used in the US and the emissions often contaminated soil near heavily traveled roads.
  • Lead piping and solder – Home water supplies that contain lead piping or that use lead solder are common in older homes. Lead can leach into standing or warm water. It is recommended before using water for drinking or food preparation for the first time in the morning, to run cold water for 2 minutes before using it.
  • Occupational exposure – parents working as a painter, welder, foundry worker, home renovator, battery plant, sheet or scrap metal or plumber or other occupations may have contaminated clothing that the child is exposed to.
  • Recreational exposure – parents working with leaded glass or ceramics may expose their children.
  • Unglazed ceramics and lead crystalware – certain ceramics and crystalware may contain lead and it can leach into the food and liquids placed into these containers. The child then eats or drinks the food and liquids and is exposed. The leaching of the lead is increased if acidic food is placed into them (e.g. orange juice) or the food item remains in the container for a long time.
  • Candy and medications – candy, medications or folk remedies purchased in other countries, often Mexico, may contain lead.
  • Art supplies – all art supplies in the US must be certified as non-toxic to be sold. Supplies purchased in other countries may not be non-toxic.

Low risk children are usually screened for lead at 12 and 24 months. High risk children are usually screened for lead at 12, 18, 24 months and at 3, 4, and 5 years or age. Fingerstick blood samples are often used but can be contaminated. Venous blood levels are used for confirmation and to monitor the child. The FDA has recently certified a new portable, easy-to-use, finger-stick test which gives results in 3 minutes and is comparable to a full laboratory testing.

Iron deficiency anemia and lead poisoning can occur separately but often occur concomitantly.

Learning Point

Normal hemoglobin has 3 components: iron (Fe+2, an element), heme (an organic molecule), and globin (a protein molecule).
Problems in any of these 3 components can lead to a variety of disease states including porphyrias and thalassemias.
Lead interferes with early steps in heme synthesis leading elevations of erythrocyte protoporphyrin, zinc protoporphyrin (ZPP), and d-aminolevulinate (which is neurotoxic). ZPP is sometimes used as a screening test for lead.
The final step in heme synthesis is the addition of Fe+2 to the finished heme molecule.

Questions for Further Discussion
1. What are the recommended treatments for lead and at what level should they be instituted?
2. What is the recommended treatment for iron deficiency anemia?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed for Lead Poisoning
and PubMed for Iron Deficiency Anemia.

Information prescriptions for patients can be found at MedlinePlus for these topics: Lead Poisoning and Anemia
and at Pediatric Common Questions, Quick Answers for these topics: Lead Poisoning and Iron Deficiency Anemia

To view current news articles on this topic check Google News for Lead Poisoning
and Google News for Iron Deficiency Anemia.

Rudolph CD, Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:368-371,1525-1528.

Diwan JJ. Molecular Biochemistry II. Synthesis of Heme. Rensselaer Polytechnic Institute. Available from the Internet at: 2005, cited 9/21/06).

Early and Periodic Screening Diagnosis and Treatment (EPSDT) Care for Kids Newsletter. The Effects of Lead Exposure on School Performance. 2006;13(2). (rev. Spring 2006, cited 9/21/06).

U.S. Food and Drug Administration Press Release. FDA Broadens Access to Lead Screening Test That Gives Immediate Results. Available from the Internet at: (rev. 9/18/06, cited 9/21/06).

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.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    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
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.

  • Professionalism
    20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    October 23, 2006