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目的分析婴儿恶性石骨症(IMO)的临床特点、致病基因、治疗及预后,加深对本病的认识。方法回顾性分析同患IMO兄妹2例的临床资料,对患儿及其父母进行目标基因测序,并复习国内外有关IMO病例资料,总结该病的临床特点和治疗方法。结果该兄妹分别于生后第7天和3天出现低钙性抽搐,X线检查提示全身骨密度增加,临床诊断为IMO。基因测序显示2例均为TCIRG1-c.1371(E12)Del C(p.457,T>Tfs71)纯合突变,妹妹还伴CLCN7-c.1919G>A(E21)(p.640,R>Q)杂合突变。文献检索纳入223例IMO病例,国内118例(包括本研究2例)、国外105例。临床症状包括贫血(64.1%)、视力障碍(50.2%)、肝脾肿大(47.1%)、生长发育迟缓(37.6%)、血小板下降(23.8%)、合并感染(19.3%)、颅骨异常(15.7%)、低血钙(10.8%)和脑积水(9.9%)。65例(其中国外56例,国内9例)基因测序发现6种致病基因,包括TCIRG1(43.1%)、RANK和RANKL(21.5%)、SNX10(21.5%)、OSTM1(9.2%)和CNCL7(4.6%),国内9例全部为TCIRG1基因突变。61例行造血干细胞移植,移植后死亡14例。结论 TCIRG1基因纯合突变是该兄妹IMO的致病原因。贫血、视力障碍、肝脾肿大是本病的主要临床症状。TCIRG1基因突变是导致IMO最常见原因,尤其在我国多见。骨髓移植是根治IMO的唯一方法。
Objective To analyze the clinical features, pathogenic genes, treatment and prognosis of infantile malignant osteoporosis (IMO) and to deepen the understanding of this disease. Methods Retrospective analysis of the clinical data of 2 brothers and sisters with IMO in our hospital, sequencing the target gene of children and their parents, reviewing the data of IMO cases at home and abroad, and summarizing the clinical features and treatment of the disease. Results The siblings showed hypocalciuric convulsions on the 7th day and the 3rd day after birth respectively. The X-ray examination showed that the whole body BMD increased and the clinical diagnosis was IMO. The results of sequencing showed that both of the two cases were homozygous for TCIRG1-c.1371 (E12) Del C (p.457, T> Tfs71) and their sister had CLCN7-c.1919G> A (E21) Q) heterozygous mutation. The literature search included 223 IMO cases, including 118 cases in China (including 2 cases in this study) and 105 cases in other countries. Clinical symptoms include anemia (64.1%), visual impairment (50.2%), hepatosplenomegaly (47.1%), growth retardation (37.6%), thrombocytopenia (23.8%), coinfection (19.3% 15.7%), hypocalcemia (10.8%) and hydrocephalus (9.9%). Six of the 65 genes (56 in China and 9 in China) were sequenced and found to be 6 pathogenic genes including TCIRG1 (43.1%), RANK and RANKL (21.5%), SNX10 (21.5%), OSTM1 4.6%), all 9 cases of domestic TCIRG1 gene mutation. 61 cases of hematopoietic stem cell transplantation, 14 died after transplantation. Conclusion The homozygous mutation of TCIRG1 gene is the causative agent of this sibling IMO. Anemia, visual impairment, hepatosplenomegaly is the main clinical symptoms of the disease. TCIRG1 gene mutation is the most common cause of IMO, especially in our country. Bone marrow transplantation is the only way to cure IMO.