Gu Hao, Mou Wenjun, Chen Zhenping, Xie Xingjuan, Yao Jiafeng, Zhang Rui, Wu Runhui, Gui Jingang
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Pediatr. 2023 Jan 18;10:1014249. doi: 10.3389/fped.2022.1014249. eCollection 2022.
DiGeorge Syndrome (DGS) is a rare disease associated with 22q11.2 chromosomal microdeletion, also known as a velocardiofacial syndrome, based on the frequent involvements of the palate, facial, and heart problems. Hematologic autoimmunity is rare in DGS but presents with a refractory course and poor prognosis. Herein, we report a case of partial DGS in a patient with refractory immune cytopenia and autoimmune lymphoproliferative syndrome (ALPS)-like manifestations.
A 10-year-old boy with growth retardation presented initially with a ventricular septal defect at 7 months old, which had been repaired soon after. The patient suffered from thrombocytopenia and progressed into chronic refractory immune thrombocytopenia (ITP) at 30 months old. One year later, the patient developed multilineage cytopenias including thrombocytopenia, neutropenia, and anemia. First-line treatment of ITP, like high-dose dexamethasone and intravenous immunoglobulin, had little or short-term effect on controlling symptoms. Whole-exome sequencing revealed the presence of a heterozygous 2.520 Mb deletion on chromosome 22q11.21. Moreover, decreased proportion of naive T cells and elevated double-negative T cells were found. The patient was given sirolimus therapy (1.5 mg/m, actual blood concentration range: 4.0-5.2 ng/ml) without adding other immunosuppressive agents. The whole blood cell count was gradually restored after a month, and the disease severity was soothed with less frequency of infections and bleeding events. Decreased spleen size and restrained lymph node expansion were achieved after 3-month sirolimus monotherapy.
This case is the first description on the efficacy of sirolimus monotherapy to treat refractory multilineage cytopenias of DGS presented with ALPS-like features.
迪格奥尔格综合征（DGS）是一种与22q11.2染色体微缺失相关的罕见疾病，也被称为腭心面综合征，因为常出现腭部、面部和心脏问题。血液系统自身免疫在DGS中较为罕见，但病程难治且预后不良。在此，我们报告一例部分性DGS患者，其患有难治性免疫细胞减少症及自身免疫性淋巴增殖综合征（ALPS）样表现。
一名发育迟缓的10岁男孩，7个月大时最初被诊断为室间隔缺损，随后不久进行了修复。该患者在30个月大时出现血小板减少，并进展为慢性难治性免疫性血小板减少症（ITP）。一年后，患者出现多系血细胞减少，包括血小板减少、中性粒细胞减少和贫血。ITP的一线治疗，如大剂量地塞米松和静脉注射免疫球蛋白，对控制症状几乎没有效果或只有短期效果。全外显子测序显示22q11.21染色体上存在杂合性2.520 Mb缺失。此外，还发现初始T细胞比例降低和双阴性T细胞升高。该患者接受了西罗莫司治疗（1.5 mg/m，实际血药浓度范围：4.0 - 5.2 ng/ml），未添加其他免疫抑制剂。一个月后全血细胞计数逐渐恢复，疾病严重程度得到缓解，感染和出血事件的发生频率降低。西罗莫司单药治疗3个月后，脾脏大小减小，淋巴结肿大得到抑制。
本病例首次描述了西罗莫司单药治疗具有ALPS样特征的DGS难治性多系血细胞减少症的疗效。
