Name: Immunodeficiency 46 | Acronym: IMD46
Alt. names: combined immunodeficiency by TfR1 deficiency

Gene: TFRC | MOI: Autosomal recessive | Mechanism of action:

No. of cases in DB: 0 | First reported in: 2016

Last updated on: 2024-02-02 09:08:16 by Andrés Caballero-Oteyza

OMIM: 616740

Orphanet: -

MONDO: -

DOID: -

ClinGen:

This condition was first described in 2016 in one large highly consanguineous Kuwaiti family with 14 affected children. All had a history of severe infections in childhood, which led to the death of 6 of them. The family was found to carry a missense (p.Tyr20His) mutation segregating with disease. This same mutation was also identified in a 5-year boy (with a similar presentation) from a consanguineous family in western Saudi Arabia; and haplotype analysis suggested a founder effect. Immunological workup uncovered hypo- to agammaglobulinemia, normal lymphocyte counts, intermittent thrombocytopenia and neutropenia, mildly low hemoglobin and low MCV, and mild iron-resistant anemia (PMIDs: 26642240). In 2024 a second missense mutation (p.R22W) was reported in a Turkish boy diagnosed with combined immunodeficiency, who presented with ITP, recurrent sinopulmonary infections, chronic diarrhea, bronchiectasis, microcytic anemia, chronic recurrent neutropenia and hypogammaglobulinemia (PMID: 38270687).

HSCT was described to resolve clinical and laboratory abnormalities (PMIDs: 26642240)