A gain-of-function mutation of STAT1 in a 3-year-old child with chronic mucocutaneous candidiasis and autoimmune hepatitis: a case report

Abstract

Background Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of primary immunodeficiency diseases (PID) characterized by chronic and recurrent infections of the skin, nails, and oropharynx, mostly caused by Candida sp. CMC is often associated with autoimmune and endocrine disorders. However, CMC may be the only or the main phenotype in patients with AD IL-17F and AR IL-17RA deficiencies, as well as gain-of-function (GOF) mutations of STAT1. Methods Case report - we describe a 3-year-old female child with a history of chronic candidiasis since 11 days of age (oral, genital, skin and nails), as well as several episodes of acute otitis media. The patient also presented local reaction to BCG. Her mother had systemic lupus erythematosus and CMC. Evolution: At 2 years of age the patient developed recurrent fever, hepatomegaly, jaundice, dark urine and abdominal distension. She was hospitalized and diagnosed with overlapping cholangitis and autoimmune hepatitis. The laboratory evaluation showed progressive increase of liver aminotransferases; presence of nodules in the spleen, infectious bronchiolitis and maxillary sinusopathy (all by CT scan), and esophageal candidiasis. The patient was treated with amphotericin, corticosteroids, antibiotics and azathioprine, and she had progressive improvement of general state and of the symptoms. She was discharged with fluconazole and azathioprine continuously; she maintains little skin and nails lesions. Results Immunoglobulins complement and lymphocytes subpopulations were normal. A genetic analysis was performed and revealed a GOF heterozygous mutation in STAT1coiled-coin domain NM_007315: exon 1:C.G821: pR274Q.