Liu Lingling, Huang Yuan, Liao Yi, Shu Sainan
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Pediatr. 2023 Jan 6;10:990729. doi: 10.3389/fped.2022.990729. eCollection 2022.
Chronic mucocutaneous candidiasis (CMC) is a heterogeneous primary immunodeficiency disease characterized by chronic or recurrent infections of the skin, nails, and mucosa and is mostly associated with STAT1 gain-of-function (GOF) mutation (GOF-STAT1 mutation).
A two-year-old girl was presented with recurrent liver dysfunction, oral candidiasis, acute bronchial pneumonia, and cytomegalovirus infection. Even after a series of treatments, including antifungal voriconazole, nystatin treatment for oral , antibiotics against bacterial infection, and bicyclol to protect the liver, the child still exhibited signs of splenomegaly. Although we performed relevant etiological tests on the child and conducted histopathology and electron microscopic examination of the liver, we could not explain the clinical symptoms. So, a genetic test was conducted to clarify the diagnosis. Since the child suffered recurrent fungal infections, we speculated that she had combined immunodeficiency. Therefore we performed high-precision clinical display PLUS detection and found that the transcription factor STAT1 had a heterozygous GOF mutation (. R274W) in its coiled-coil domain.
The clinical manifestations of chronic mucocutaneous candidiasis caused by GOF-STAT1 mutations are complex and range from mild local fungal infections to severe systemic diseases and are sometimes fatal. Clinicians need to be aware of the possibility of this disease in children with recurrent fungal infections for early diagnosis and treatment.
慢性黏膜皮肤念珠菌病（CMC）是一种异质性原发性免疫缺陷疾病，其特征为皮肤、指甲和黏膜的慢性或复发性感染，且大多与信号转导和转录激活因子1（STAT1）功能获得性（GOF）突变（GOF-STAT1突变）相关。
一名两岁女童出现反复肝功能障碍、口腔念珠菌病、急性支气管肺炎和巨细胞病毒感染。即便接受了一系列治疗，包括抗真菌的伏立康唑、口腔用制霉菌素治疗、针对细菌感染的抗生素以及用于保护肝脏的双环醇，该患儿仍表现出脾肿大迹象。尽管我们对患儿进行了相关病因学检查，并对肝脏进行了组织病理学和电子显微镜检查，但仍无法解释其临床症状。因此，进行了基因检测以明确诊断。由于该患儿反复发生真菌感染，我们推测她患有联合免疫缺陷。于是我们进行了高精度临床表型PLUS检测，发现转录因子STAT1在其卷曲螺旋结构域存在杂合性GOF突变（.R274W）。
GOF-STAT1突变所致慢性黏膜皮肤念珠菌病的临床表现复杂，从轻度局部真菌感染到严重的全身性疾病不等，有时甚至会致命。临床医生需要意识到反复发生真菌感染的儿童患此病的可能性，以便早期诊断和治疗。
