What causes low ferritin
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Causes of Low Ferritin Levels
Celiac Disease and Low Ferritin
Celiac disease (CD) is a significant cause of low ferritin levels. CD is a genetic disorder that impairs nutrient absorption in the small intestine, leading to iron deficiency. Studies have shown that patients with restless legs syndrome (RLS) and low serum ferritin often have undiagnosed CD. In a case series, four patients with RLS and serum ferritin levels below 25 ng/mL were found to have CD, confirmed by duodenal biopsy. Treatment with a gluten-free diet improved their ferritin levels and RLS symptoms .
Genetic Hemochromatosis and Ferritin Synthesis
Genetic hemochromatosis (GH) is another condition affecting ferritin levels. GH is characterized by low expression of duodenal ferritin due to a defect in ferritin synthesis. Research indicates that in GH patients, ferritin gene transcription is preserved, but the accumulation of ferritin is low due to reduced expression of ferritin messenger RNA and increased activity of the iron regulatory factor .
Mutations in the L-Ferritin Gene
Mutations in the L-ferritin gene (FTL gene) can lead to low ferritin levels. These mutations cause conditions such as neuroferritinopathy and autosomal dominant or recessive L-ferritin deficiency. Patients with these genetic mutations exhibit low serum ferritin levels despite normal levels of other iron parameters. For instance, a specific missense mutation (c.473T > C; p.Pro158Leu) in the FTL gene was identified in two sisters with low serum ferritin but normal iron levels, indicating that the mutation affects ferritin's ability to store iron Cadenas2019Çiftçiler2020.
Iron Deficiency and Restless Legs Syndrome
Iron deficiency is a well-known cause of low ferritin levels and is closely associated with restless legs syndrome (RLS). A meta-analysis revealed that low serum ferritin levels are significantly associated with the augmentation of RLS symptoms. Iron supplementation can alleviate RLS symptoms and reduce the risk of augmentation, highlighting the importance of maintaining adequate ferritin levels in these patients Levi2015Li2023.
Inflammation and Ferritin Levels
Inflammation can also influence ferritin levels. Ferritin is an acute-phase protein that increases during inflammation, which can mask underlying iron deficiency. Studies have shown that inflammation can increase ferritin levels by up to 49.6%, leading to an underestimation of iron deficiency. Therefore, it is crucial to adjust ferritin measurements for inflammation markers like C-reactive protein (CRP) and alpha(1)-acid glycoprotein (AGP) to accurately assess iron status Thurnham2010Moen2018.
Conclusion
Low ferritin levels can result from various conditions, including celiac disease, genetic hemochromatosis, mutations in the L-ferritin gene, iron deficiency, and inflammation. Understanding these underlying causes is essential for accurate diagnosis and effective treatment. Regular screening for conditions like CD and adjusting ferritin measurements for inflammation can help manage and prevent complications associated with low ferritin levels.
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Most relevant research papers on this topic
Celiac disease as a possible cause for low serum ferritin in patients with restless legs syndrome.
Celiac disease may cause low serum ferritin in patients with restless legs syndrome, and diagnosis and treatment of CD may improve their RLS symptoms and identify individuals at risk for long-term complications.
Duodenal ferritin synthesis in genetic hemochromatosis.
In patients with genetic hemochromatosis, low duodenal ferritin accumulation is caused by low expression of ferritin messenger RNA and sustained activity of iron regulatory factor, not defective control of ferritin synthesis.
L-Ferritin: One Gene, Five Diseases; from Hereditary Hyperferritinemia to Hypoferritinemia—Report of New Cases
Defects in the L-ferritin gene cause various diseases, including hereditary hyperferritinemia with cataract syndrome and neuroferritinopathy, and accurate diagnosis is crucial for effective treatment.
A unique mutation in the L ferritin coding sequence associated with low serum ferritin level in the presence of normal values of other iron parameters.
This study identified a unique mutation in the FTL gene, causing low serum ferritin levels in individuals with normal iron parameters, suggesting ferritin connects iron but cannot store it.
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