Human FCHO1 deficiency - Review of the Literature and Additional Two Cases.

F-BAR domain only protein 1(FCHO1) contributes as a critical component to an essential cellular process, clathrin-mediated endocytosis(CME). CME involves cellular membrane invagination followed by cargo protein recruitment and adaptor protein assembly to form endocytic vesicles, maintains several cellular functions, such as signaling, differentiation, nutrition, absorption, and secretion. We aimed to determine the clinical/immunological findings in FCHO1 deficiency to generate appropriate medical approach. We present clinical/immunological/genetic findings of two FCHO1 deficiency patients together with recently reported 17 patients. We found two different variants in the patients, one previously defined and one novel homozygous mutation(c.306C>A(p.Tyr102Ter)). Recurrent sinopulmonary infections occurred in all patients, with viral(63.1%) and fungal(52.6%) infections frequently reported. Lymphopenia and CD4+T cell lymphopenia are present in 77.7%(14/18) and 100% of patients, respectively. CD8+ T cell number is low in half. Hypogammaglobulinemia and low IgM are present in 83.3%(15/18) and 61.1%(11/18) of patients, respectively. Neurological disorders(Guillian-Barre Syndrome, Moya Moya disease, encephalitis, and cranial infarction) are common(n=6(31.5%)). Malignancy is present in four(21%) patients, three suffered from diffuse large B cell lymphoma and one developed Hodgkin lymphoma. Additional clinical and laboratory results from more patients helped to define the characteristics of FCHO1 deficiency. The early application of molecular genetic analysis in CID patients is crucial. Since all transplanted patients were alive, allogeneic hematopoietic stem cell transplantation emerged as a potential curative therapy.