Sickle Cell Disease (SCD) has variable clinical manifestations, resulting from hemolytic anemia, vaso-occlusion, and an inflammatory process, causing acute or chronic pain and organ damage. We aimed to report the clinical case of fraternal twin's carriers of the S-beta-thalassemia.

Clinical case report involving twin brothers and sister, black, from the city of Óbidos, state of Pará, Brazil, currently residing in Manaus-Amazonas, Brazil. Accompanied since the age of 10, with molecular diagnosis for S-beta-Thalassemia.

The 1st male twin, FPS, 34 years old, black, works as a freelancer, has a mild to moderate clinical condition and does not need transfusions and/or hospitalizations. He does not use hydroxyurea. Her last hemoglobin profile showed a concentration of 13.7% HbFetal and 5.1% for HbA2. The 2nd male twin, VPS, 34-years old, black ethnicity, farmer, has had painful crises since childhood, with a history of several hospitalizations, mainly due to splenomegaly and splenectomy performed at 5-years of age. He has cholelithiasis and underwent cholecystectomy at the age of 22. He started using Hydroxyurea only at the age of 23, with significant improvement in symptoms and in the intensity and frequency of vaso-occlusive events. Her last hemoglobin profile showed a concentration of 22.6% to HbFetal and 4.9% for HbA2. The sister, CPS, 41-years old, black, works as a housemaid, was only diagnosed when she was 17-years old. She reported three miscarriages and one high-risk pregnancy at age 24 (with the HbAS trait). She currently has several painful crises/year, mainly pain in the lower limbs, aseptic necrosis of the femoral head, malleolar ulcer for over 15-years, with two blood transfusions/year. She has been using Hydroxyurea for 10-years. Her last hemoglobin profile showed a concentration of 16.9% for HbFetal and 5.3% for HbA2.

The clinical variability of SCD, even in twins, has very different clinical manifestations, with several direct and indirect factors that modulate the manifestations, whether hematological, biochemical, inflammatory or genetic biomarkers, in addition to socioeconomic and demographic characteristics.