Name: Immunodeficiency 99 | Acronym: IMD99
Alt. names: CTNNBL1 deficiency | Immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias

Gene: CTNNBL1 | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 1 | First reported in: 2020

Last updated on: 2023-10-23 05:19:37 by Xiao P. Peng

OMIM: 619846

Orphanet: -

MONDO: 0030798

DOID: -

ClinGen:

In the sole example of this condition described in the literature thus far, Kuhny et al. (2020) identified a homozygous CTNNBL1 missense variant (c.1396A>G, p.M466V) in a 15-yo girl born to nonconsanguineous parents who presented in early life with recurrent steroid-resistant immune thrombocytopenia, vitiligo, lymphadenopathy, and recurrent sinopulmonary infections (PMID: 32484799). Immunophenotyping was notable for severe progressive hypogammaglobulinemia and B and T cell lymphopenia, while lymph node biopsy pathology showed hyperplastic germinal centers. The patient had absent switched memory B cells consistent with evidence of defective class-switch recombination (CSR) and somatic hypermutation (SHM). She also showed T cell abnormalities in the form of decreased Treg and increased follicular helper-like T cell proportions, as well as poor T cell proliferation in response to PHA.

The single patient described above required romiplostim to treat her steroid-resistant thrombocytopenia and ongoing immunoglobulin replacement therapy for progressive severe hypogammaglobulinemia; however, her vitiligo and growth delay eventually resolved.