5例STAT1功能获得性基因突变儿童慢性皮肤黏膜念珠菌病临床特点及生化免疫分析

Clinical characteristics and biochemical immunoassay of chronic mucocutaneous candidiasis due to gain-of-function mutations in STAT1 in 5 children

目的分析STAT1功能获得性儿童慢性皮肤黏膜念珠菌病(CMC)的临床特点、生化及免疫学检查结果。方法回顾分析2016—2019年经基因检查确诊的5例CMC患儿的临床资料。结果5例患者,男4例,女1例,平均发病年龄(4.2±3.6)月龄(1~10月龄)。5例患儿均有黏膜感染,4例反复呼吸道感染,4例皮肤感染,3例指趾甲反复念珠菌感染,2例桥本甲状腺炎,甲状腺功能低下、甲状旁腺功能减低、肾上腺皮质功能减退、矮小症各1例。5例患儿基因突变位点均为STAT1,分别为c.849G>T、c.988C>A、c.862A>G、c.1154C>T、c.974T>A。5例患儿的IgG、IgE无异常,2例IgA、IgM降低明显。CD3+细胞减少;CD3+CD4+细胞减少、CD19细胞明显减少各1例。5例患儿的血细胞计数均无异常,2例抗甲状腺球蛋白抗体、抗甲状腺过氧化酶抗体明显增高,甲状旁腺激素降低、皮质醇降低各1例。2例G试验阳性,但无侵袭性真菌感染表现。结论反复皮肤、黏膜、指趾甲念珠菌感染是CMC的重要临床表现,免疫功能筛查有提示意义,须基因检测才能确诊。

Objective To explore the clinical features, biochemical and immunological findings of chronic mucocutaneous candidiasis (CMC) due to gain-of-function mutations in STAT1 in children. Method The clinical data of CMC in 5 children diagnosed by genetic examination from 2016 to 2019 were retrospectively analyzed. Results In 5 patients (4 males, 1 female) the mean age at onset was 4.2±3.6 months (1-10 months). The mucosal infection was found in all of 5 cases, recurrent respiratory tract infection in 4 cases, skin infection in 4 cases, repeated candidiasis of fingernails and toenails in 3 cases, Hashimoto's thyroiditis in 2 cases, and hypothyroidism, hypoparathyroidism, hypoadrenocorticism and dwarfism in one case each. The gene mutation sites of the 5 children were all located in STAT1, which were c.849G >T, c.988C >A, c.862A > G, c.1154C >T, and c.974T >A, respectively. IgG and IgE were normal in 5 cases, and IgA and IgM were significantly reduced in 2 cases. One patient had decreased CD3+ cells, 1 patient had decreased CD3+CD4+ cells, and 1 patient had significantly decreased CD19 cells. Decreased CD3+ cells, CD3+CD4+ cells and CD19 cells were found in one case each. There was no abnormality in the blood cell count of the 5 children, There were the significantly increased anti-thyroglobulin antibody and anti-thyroid peroxidase antibody in 2 cases, and the decreased parathyroid hormone in 1 case and decreased cortisol in 1 case. Two cases were positive in G test, but no invasive fungal infection was found. Conclusions Repeated Candida infection of skin, mucosa and nails is an important clinical manifestation of CMC. Screening of immune function is suggestive, and gene testing is required to confirm the diagnosis.