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Updated: Aug 12, 2026

Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Elevated zinc protoporphyrin associated with thalassemia trait and hemoglobin E
E A Graham1, J Felgenhauer, J C Detter
1Department of Pediatrics, University of Washington, Seattle, USA.
The zinc protoporphyrin/heme (ZPP/H) ratio is elevated in hereditary hemoglobin disorders like thalassemia, even without iron deficiency. Persistent high ZPP/H ratios in children treated for iron deficiency may signal these underlying conditions.
Area of Science:
- Hematology
- Medical Diagnostics
- Genetics
Background:
- The zinc protoporphyrin/heme (ZPP/H) ratio is a screening tool for iron deficiency and lead poisoning in children.
- Hereditary hemoglobin disorders, such as alpha- and beta-thalassemia traits and hemoglobin E, are prevalent in U.S. minority populations.
- These disorders can present with microcytic anemia, mimicking iron deficiency.
Purpose of the Study:
- To investigate the association between common hereditary hemoglobin disorders and elevated ZPP/H ratios in iron-sufficient individuals.
- To determine if ZPP/H ratio can help differentiate hereditary hemoglobinopathies from iron deficiency.
Main Methods:
- A retrospective analysis of hemoglobinopathy screening data from 1987-1993.
- Included 326 iron-sufficient subjects (serum ferritin > or = 50 micrograms/L) aged 15-49 years.
- Measured ZPP/H ratio and hemoglobin type.
Main Results:
- Significantly higher mean ZPP/H ratios were observed in subjects with beta-thalassemia trait (87 +/- 32), alpha-thalassemia trait (73 +/- 37), and hemoglobin E (73 +/- 24) compared to normal hemoglobin (60 +/- 8).
- Elevated ZPP/H ratios (> 80 micromol/mol) were found in 51% of beta-thalassemia trait, 22% of hemoglobin E, and 20% of alpha-thalassemia trait subjects.
- Only 1.5% of subjects with normal hemoglobin had elevated ZPP/H ratios.
Conclusions:
- The ZPP/H ratio is elevated in hereditary hemoglobin disorders that mimic iron deficiency anemia, irrespective of iron status.
- A persistently elevated ZPP/H ratio in children treated for presumed iron deficiency, especially with ongoing microcytosis, suggests a possible hereditary hemoglobin disorder.
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