STAT1 gain of function (STAT1 GOF) is a congenital disorder characterized by a broad clinical spectrum, with chronic mucocutaneous candidiasis as the more common phenotype. We report a patient diagnosed with STAT1 GOF.
The immunophenotype and functional assays were analyzed by flow cytometry, the genetic study was performed by a NGS customized panel containing all the immunodeficiency diseases-related genes and the result was confirmed by Sanger sequencing.
The patient a 31-year-old woman, who at 18 months, suffered persistent candida infections refractory to the antifungal treatment. During her childhood presented pneumonia, herpes-zoster infection and several sinusitis as the main infectious processes. Moreover, severe osteopenia was detected. The patient needed GH treatment due to a failure to thrive associated with malabsorption syndrome and chronic hepatitis. At 15 years old, premature menopause and ovary failure were detected. In 2017 the genetic study showed a heterozygous variant, c.1885C>T (p.H629Y), in STAT1 gene. Functional assays showed a dephosphorylation defect in STAT1p, and elevated Th1/Th17 ratio was found, therefore the patient was diagnosed with STAT1 GOF. Currently, her recurrent respiratory infections have improved, however, autoimmune processes became a serious problem. A few years ago she developed a vasculopathy and hidradenitis suppurativa with an infectious and autoinflammatory component.
Given the complexity of clinical manifestation in these patients, treatments are widely varied: prophylaxis of infections, antifungals, immunosupressive drugs, and immunoglobulins. Recently, ruxolitinib has been proposed as a new option with encouraging results.