ABSTRACT
PURPOSE: Combined immunodeficiency (CID), due to mutations in TFRC gene that encodes the transferrin receptors (TfR1), is a rare monogenic disorder. In this study, we further characterize the clinical and immunological phenotypes in a cohort of eight patients. METHODS: A retrospective review of clinical and immunological features of patients diagnosed with a TFRC gene mutation between 2015 and 2019 in three tertiary centers. RESULTS: Eight patients from six unrelated families were enrolled. The patients had a median age of 7 years (4-32 years). All patients presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life. Less common features were skin abscesses, conjunctivitis, global developmental delay, optic nerve atrophy, vitiligo, multinodular goiter, and hemophagocytic lymphohistiocytosis-like symptoms. All patients had intermittent neutropenia and 87% of the patients had recurrent thrombocytopenia. Anemia was found in 62%. All patients had hypogammaglobinemia and one had a persistent high IgM level. All patients had impaired function of T cells. The same homozygous missense mutation c.58T>C:p.Y20H, in the TFRC gene, was detected in all patients. Stem cell transplantation from matched donors was successful in two patients. Five patients did not receive stem cell transplantation, and they are on prophylactic treatment. One patient died due to severe sepsis and neurological complications. CONCLUSION: This report provides a large cohort with a long follow up of patients with this disease. Our cohort showed variable disease severity.