Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive intestinal absorption of iron and progressive iron overload. Clinical features may include hepatomegaly, cirrhosis, diabetes, cardiomyopathy, hypogonadism, and arthropathy. Diagnosis is based on transferrin saturation, serum ferritin, and confirmation by genetic testing. We present two siblings with homozygous HFE gene mutation who showed marked hyperferritinemia and a favorable response to oral deferasirox therapy.

A 40-year-old male presented to the hematology outpatient clinic on January 17, 2025, with elevated ferritin levels. His 48-year-old brother had been diagnosed with primary hereditary hemochromatosis in 2011. The elder sibling was treated with oral desferrioxamine (1 × 3 tablets daily) for several years but discontinued therapy in 2020 and remained untreated thereafter.

Genetic analysis demonstrated that both siblings carried the HFE c.187C>G (p.His63Asp) homozygous mutation. At presentation, the proband’s serum ferritin level was 1845 ng/mL, while his brother’s level exceeded 1600 ng/mL. Both patients were started on oral deferasirox at a dose of 20 mg/kg/day (1 × 6 tablets). Regular laboratory follow-up was conducted every 4–6 weeks.

After initiation of deferasirox, both siblings demonstrated significant biochemical improvement.

• The proband’s ferritin decreased from 1845 ng/mL to 1090 ng/mL within three months.

• The elder sibling’s ferritin declined from >1600 ng/mL to 945 ng/mL in the same period.

Both patients tolerated the medication well, without major adverse events. No hepatic decompensation, cardiac dysfunction, or endocrine complications were observed during follow-up.

This familial case illustrates several important points. First, family history and genetic testing remain critical tools in early recognition of hereditary hemochromatosis. The diagnosis in the younger sibling was established promptly because of the known history in his elder brother. Second, although phlebotomy remains the standard of care in HH, oral iron chelators such as deferasirox may be effective alternatives, particularly in patients where phlebotomy is less feasible. In both siblings, ferritin levels declined substantially with deferasirox monotherapy. Third, interruption of treatment, as seen in the elder sibling, allows ferritin to rise again, underlining the importance of sustained long-term management.

We report two siblings with homozygous HFE-related hereditary hemochromatosis and significant hyperferritinemia. Both responded favorably to deferasirox therapy with substantial reductions in ferritin levels. These findings emphasize the value of family screening, genetic testing, and consistent treatment in the management of hereditary hemochromatosis.