Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×109/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
目的： 探讨婴儿恶性石骨症患儿的临床特征和遗传学特点。 方法： 回顾性病例分析。选择2013年1月至2022年9月就诊于首都医科大学附属北京儿童医院的37例婴儿恶性石骨症患儿为研究对象，根据患儿基因突变位点将患儿分为CLCN7组和TCIRG1组，分析两组患儿临床特点、实验室检查及预后的差异。组间比较采用Wilcoxon秩和检验或Fisher精确检验，使用Kaplan-Merier法绘制生存曲线，Log-Rank法进行组间比较。 结果： 37例患儿男22例、女15例。诊断时年龄0.5（0.2，1.0）岁。CLCN7基因突变13例（35%），TCIRG1基因突变24例（65%）。CLCN7基因突变组患儿诊断时年龄［1.2（0.4，3.6）比0.4（0.2，0.6）岁，Z=-2.60，P=0.008］、起病时血磷［1.7（1.3，1.8）比1.1（0.8，1.6）mmol/L，Z=-2.59，P=0.010］、肌酸激酶同工酶（CK-MB）［457（143，610）比56（37，82）U/L，Z=-3.38，P=0.001］、白细胞计数水平［14.0（9.9，18.1）比9.2（6.7，11.1）×109/L，Z=-2.07，P=0.039］均高于TCIRG1基因突变组；CLCN7组起病时D二聚体［2.7（1.0，3.1）比6.3（2.5，9.7）μg/L，Z=2.83，P=0.005］低于TCIRG1组。接受造血干细胞移植后，两组患儿5年总生存率差异无统计学意义［（92.3±7.4）%比（83.3±7.6）%，χ²=0.56，P=0.456］。 结论： 婴儿石骨症患儿以TCIRG1基因突变更常见，有此基因突变的患儿发病年龄小、发病初期血磷、CK-MB、白细胞计数水平低，但D二聚体水平高。不同基因型患儿行造血干细胞移植后预后相似。.