Screening for hemochromatosis by measuring FERRITIN levels

Because the penetrance of HFE hemochromatosis is low, traditional population screening measuring the transferrin saturation is unlikely to be cost-effective, as the vast majority of individuals detected neither have clinical disease nor are likely to develop it.

Three independent studies show that only patients with serum ferritin concentrations over 1000 ng/ml are at risk for cirrhosis , one of the main morbidities of hemochromatosis. Among 29,699 white subjects participating in the Scripps-Kaiser hemochromatosis study, only 59 had serum ferritin levels of greater than 1000 ng/ml. Twenty-four had homozygous mutant or compound heterozygous mutant HFE genotypes .

In all but 5 of the other subjects the causes of elevated ferritin was excessive alcohol intake, cancer, or liver disease. Screening for hemochromatosis with serum ferritin levels will detect the vast majority of patients who will be clinically affected, and may detect other clinically significant disease in patients who do not have hemochromatosis genotypes .

Since it is clear that the ferritin level of the vast majority of adult homozygotes for HFE mutations does not rise over long periods of time, excluding subjects with serum ferritin levels /=1000 ng/ml should not result in missed opportunities for early treatment of patients who could benefit.

PMID: 18025154
Waalen J , Felitti VJ , Gelbart T , Beutler E .
Department of Molecular and Experimental Medicine , The Scripps Research Institute, La Jolla, CA, United States.


FERRITIN: Augmentation in restless legs syndrome -low ferritin

Background and purpose: Augmentation is a major problem with dopaminergic therapy for restless legs syndrome (RLS), and predictors of augmentation have not yet been identified. We aimed to analyze the relationship between baseline ferritin level and occurrence of augmentation in a retrospective analysis of a prospective double-blind trial of cabergoline versus levodopa on augmentation in RLS.

Patients and methods: Patients who experienced augmentation were compared to patients who did not experience augmentation.

Results: Augmentation symptoms causing premature discontinuation from the study or which were tolerated (n = 36, ferritin: 85 + 59 ng/ml) were associated with lower levels of serum ferritin compared to patients without augmentation (n = 302, ferritin : 118 + 108 ng/ml, p = 0.0062).

Conclusions: Ferritin as a marker of iron storage may play an important role in the pathophysiology of RLS and may prove to be a biomarker for the development of augmentation under dopaminergic therapy.

Keywords: Restless legs syndrome; Augmentation; Dopaminergic therapy; Ferritin; Iron storage; Cabergoline; Levodopa

Corresponding author. Address: Paracelsus-Elena Klinik, Klinikstrasse 16, 34128 Kassel, Germany. Tel.: +49 561 6009 200; fax: +49 561 6009 126.



Ferritin is a water-soluble, iron storage protein found in most animal cells. Its spherical structure is composed of 24 subunits and contains a 7-nm cavity with a ferric oxyhydroxide crystalline core that is capable of storing approximately 4500 iron atoms. Iron passes in and out of the ferritin cavity through 0.7-1.0 nm pores in the outer shell. Up to 25 ferritin isoforms are thought to exist, composed of various combinations of the two primary subunits, H and L, which have molecular weights of 21,000 and 19,000, respectively.Ferritin rich in the Heavy subunit is found in heart muscle, red blood cells, Lymphocytes and monocytes,while that rich in the Light subunit is found in the liver, spleen, and placenta.

Ferritins composed of a higher proportion of H subunits are more acidic (pI as low as 4.8) than the isoforms containing a higher proportion of L subunits (pI 5.3-5.8) Human serum ferritin is primarily composed of the L subunit, which also corresponds with a lower iron content. Liver Ferritinand Spleen Ferritin contain > 12% iron by weight accoring to published reports.

Ferritin is the body's primary iron source for Hemoglobin synthesis; only hemoglobin itself accounts for more of the body's total iron content. When serum iron levels decrease below normal levels, ferritin readily releases its iron stores for use. Serum levels of ferritin are known to closely parallel tissue ferritin levels and are, therefore, indicative of body iron content. As such, clinical tests for ferritin serum levels are used to detect and manage iron-related disorders, such as iron deficiency anemia and iron overload. In addition, high levels of serum ferritin have been associated with malignant disease and tissue damage.