Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies

Abstract EN

Chronic Mucocutaneous Candidiasis (CMC) is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails.

A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections.

Candida albicans grew in oral mucosa swab.

CMV and EBV DNA titers were elevated.

She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal.

She had parenchymal nodules within the lungs and a calcific nodule in the liver.

Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases.

Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF) (c.1154 C>T, p.Thr385Met) in the gene coding STAT1 molecule.

Hematopoietic stem cell transplantation (HSCT) was planned because of severe recurring infections.

Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings.

HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops.

This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.