Why would a young, healthy patient have hyper ferritinemia with 71% transferrin saturation?

From the Guidelines

A high iron saturation of 71% in a young, healthy patient is most likely indicative of hereditary hemochromatosis, a genetic disorder that requires prompt evaluation and treatment to prevent long-term complications, as suggested by the European Association for the Study of the Liver in their 2022 clinical practice guidelines on haemochromatosis 1. The patient's high iron saturation level is a significant concern, as it can lead to progressive iron loading and damage to various organs, including the liver. According to the guidelines, a transferrin saturation (TSAT) level above 45% in females and 50% in males is sufficient to diagnose provisional iron overload in patients homozygous for the p.Cys282Tyr mutation in the HFE gene 1. Key considerations in the evaluation of this patient include:

• Genetic testing for HFE gene mutations, particularly C282Y and H63D
• Serum ferritin and total iron binding capacity tests to assess iron overload
• Liver function tests to evaluate liver damage
• Imaging studies, such as MRI, to assess hepatic iron overload and liver fibrosis If hereditary hemochromatosis is confirmed, treatment typically involves:
• Therapeutic phlebotomy every 1-2 weeks until iron levels normalize
• Maintenance phlebotomy 2-4 times per year to prevent iron accumulation
• Limiting alcohol consumption and avoiding iron supplements or vitamin C with meals Early diagnosis and treatment are crucial to prevent complications like liver cirrhosis, diabetes, heart problems, and joint damage, as emphasized in the 2022 guidelines 1.

From the Research

Possible Causes of High Iron Saturation

• High iron saturation can be caused by various factors, including genetic disorders such as hereditary hemochromatosis 2, 3, 4
• Hereditary hemochromatosis is characterized by increased intestinal iron absorption, leading to iron overload 4
• Other conditions, such as thalassemia major, can also lead to iron overload due to frequent blood transfusions 5

Genetic Mutations and Iron Overload

• Ferroportin disease is a rare type of autosomal dominantly inherited hemochromatosis caused by mutations in the ferroportin gene (SLC40A1) 2
• Patients with ferroportin disease characteristically have hyperferritinemia but normal transferrin saturations 2
• HFE-related hereditary hemochromatosis is another condition that can lead to iron overload, and is characterized by increased intestinal iron absorption 4

Treatment Options for Iron Overload

• Phlebotomy is a common treatment for iron overload, but may not be suitable for all patients, such as those with anemia or poor venous access 3, 4
• Iron chelation therapy, such as deferasirox, can be an effective alternative treatment for iron overload 2, 3, 5, 4
• Deferasirox has been shown to reduce iron burden in patients with hereditary hemochromatosis and thalassemia major 5, 4