Homozygous TFR2 (c.2093_2096del) Mutation in an Asymptomatic Patient With Type 3 Hereditary Hemochromatosis, First...

Hereditary hemochromatosis (HH) is an inherited disorder of iron metabolism characterized by progressive iron accumulation in multiple organs. While most cases are associated with HFE mutations, non-HFE variants such as mutations in the transferrin receptor-2 (TFR2) gene represent rare causes of iron overload. We report a 37-year-old Saudi male who was incidentally found to have markedly elevated ferritin levels during routine laboratory testing. The patient was asymptomatic and was incidentally found to have significant hyperferretinemia through routine lab evaluation. Magnetic resonance imaging (MRI) demonstrated diffuse hepatic iron deposition. Furthermore, Whole exome sequencing identified a homozygous TFR2 c.2093_2096del frameshift mutation. Using these results to reach a diagnosis, the patient was treated with frequent therapeutic phlebotomies, leading to a reduction of ferritin levels. To our knowledge, this represents the first reported case of homozygous TFR2 c.2093_2096del mutation-associated hereditary hemochromatosis in Saudi Arabia. This case sheds light on the importance of considering non-HFE HH in patients with unexplained hyperferritinemia as early diagnosis ensures the prevention of long-term complications.