Name: Immunodeficiency 55 | Acronym: IMD55
Alt. names: Combined immunodeficiency due to GINS1 deficiency | Combined immunodeficiency with intrauterine growth retardation-NK cell deficiency-neutropenia

Gene: GINS1 | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 6 | First reported in: 2017

Last updated on: 2023-10-23 05:30:21 by Xiao P. Peng

OMIM: 617827

Orphanet: 505227

MONDO: 0044725

DOID: 0111993

ClinGen:

Cottineau et al. (2017) identified compound heterozygous GINS1 mutations in 5 patients from 4 families with a recessively inherited syndromic immunodeficiency characterized by intrauterine and postnatal growth retardation, recurrent viral and bacterial infections, mild facial dysmorphism, skin problems (i.e. eczema, ichthyosis, psoriasis), lymphadenopathy, autoimmunity (i.e. protein-losing enteropathy, hypothyroidism, autoimmune hemolytic anemia), malignancy (osteosarcoma in 1 patient), and some features of premature aging. Immunophenotyping was notable for G-CSF-responsive chronic neutropenia and an almost complete lack of circulating NK cells that could not be overcome by cytokine treatment, in addition to low levels of other circulating ILC and invariant T lymphocyte populations. Additionally, patient had low or normal numbers of circulating T and B cells, often with low CD8+ T cell counts, as well as high IgA levels, low IgM levels, and low to normal IgG levels. T cell proliferative responses to mitogen and antigen stimulation were slightly decreased.

Most patients received some form of anti-microbial prophylaxis, whilst two with autoimmune manifestations received immunoglobulin replacement therapy and one also received G-CSF for neutropenia. Two others received growth hormone treatment for their post-natal growth impairment. While some patients have been described to develop cancers, given the rarity of this condition, it is difficult to conclude at present whether or not there is increased malignancy risk and if so, what the level of risk and tissue spectrum of tumors may be. Thus, clinical vigilance is warranted but no guidance regarding surveillance is available.