Article Text

  1. S. Gupta,
  2. G. M. Stroh,
  3. H. Hassouna
  1. Michigan State University, East Lansing, MI.


Structural, biochemical, and physiologic similarities make it possible for manganese to directly interact with iron on enzymes and proteins that require iron as a cofactor in their catalytic center. Elegant in vitro studies by Li et al (Toxicology and Applied Pharmacology 2005;205:188-200) demonstrate that manganese treatment alters the transcriptional but not translational level of the transferrin receptor (Tfr) expression and significantly augments the influx of Fe to the choroid plexus at the blood-CSF barrier. Transferrin bound diferric iron interacts with Tfr to undergo receptor-mediated endocytosis into erythroid precursors, hepatocytes, and brain endothelial cells, and proteolytic cleavage of the extracellular Tfr segment provides an index of the iron tissue levels. Although manganese toxicity is well documented, a beneficial role for manganese on iron homeostasis in the blood and the brain has never been reported. We present a lifelong iron deficiency microcytic anemia associated with symptoms suggestive of neurotransmitter dysregulation and perceptual size distortion in a 54-year-old white female. She had a total absence of sweating, severe constipation, and intolerance to heat and cold and episodes of oculomotor bias with size underestimation lasting 15 to 20 minutes. The anemia and symptoms resolved with daily administration of 10 mg over-the-counter oral manganese supplement (manganese). Premanganese levels for haptoglobin, direct bilirubin, and immunoglobulin were within the normal range. Erythrocyte sedimentation rate and platelet and white cell counts were within the normal range. Erythropoietin levels were 11 mU/mL (ref 4-21 mU/mL). Blood transfusions but not oral iron improved her symptoms but not the red cell indices and a consistently low reticulocyte count (0.6%). She had been off oral iron for a few months prior to her visit. Manganese was started in May 2005, discontinued December to February 2006 (‡), and resumed from then until the present. Manganese-induced changes in her hematologic profile and iron status from April 2005 to November 2006 are presented in Table 1. Studies performed in March and April in 2005 show iron studies consistent with appropriate iron absorption from the gut and inefficient incorporation of iron in the erythron, possibly from decreased TfR expression. Her tissue iron stores measured by ferritin levels were negligible. Manganese significantly increased her Hgb levels and corrected the MCV but not the soluble transferrin receptor levels that remain consistently above normal, an indication of deficient iron tissue storage. She started perspiring, and her ocular symptoms did not recur. On August 6, 2006, she had significant blood loss (§) that decreased her red blood cell count to 2.8 mill/μg and created a normochromic normocytic anemia with a reticulocyte count rising to 2%, a surprising consequence of manganese. We postulate that manganese, by positively influencing Tfr expression, reversed the underlying microcytic hypochromic iron deficiency anemia and related symptoms.

Table 1

Manganese-Induced Changes in Hematologic Profile and Iron Status

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