Pentostatin for treatment of refractory autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome (ALPS), a disorder of programmed cell death, could be due to a congenital defect in the Fas signaling pathway or other pathways for apoptosis. Most cases present with lymphoproliferation and certain autoimmune features such as thrombocytopenia, neutropenia, and anemia are due to excessive production of antibodies by B lymphocytes. Majority of cases present within the first few years of life. We report a case of ALPS presenting at birth which was refractory to splenectomy and immunosuppressive therapy, but responded to pentostatin followed by hematopoietic stem cell transplantation (HSCT).     

Accessory spleen: Differential diagnosis for lymphoma in autoimmune lymphoproliferative syndrome

Mutations of Fas or, less frequently, Fas ligand genes result in a rare inherited lymphoid disorder called autoimmune lymphoproliferative syndrome (ALPS) in which lymphoma frequency is increased. We report on a patient with ALPS who had been splenectomized for giant splenomegaly and progressively developed a voluminous abdominal tumor. The histology of the removed tumor revealed that it was an accessory spleen exhibiting typical features of ALPS involvement, as shown by the presence of a large excess of CD3⁺CD4^?CD8^? T cells and plasma cells without a detectable monoclonal population. This observation highlights the lymphoma's differential diagnosis in this context. Pediatr Blood Cancer 2010;54:1020–1022 © 2010 Wiley‐Liss, Inc.     

自身免疫性淋巴增生综合征的临床表现和诊治进展

自身免疫性淋巴增生综合征（autoimmune lymphoproliferative syndrome,ALPS）是一种最近认识,因遗传性程序性细胞死亡或凋亡缺陷,导致淋巴细胞自身稳定和正常免疫耐受障碍的罕见疾病（MIM 601859）,又称Canale-Smith综合征.其特征为婴幼儿期起病,慢性、非恶性脾和淋巴结肿大,各种自身免疫临床表现,外周血罕见的CD＋3CD-4CD-8双阴性T细胞（DNT）增多,淋巴细胞体外凋亡缺陷.至2003年全球诊断约80例[1],目前国内尚未见报道,为提高临床医师对本病的认识,将ALPS的临床表现和诊治进展总结如下.     

马方综合征的最新诊疗进展北大核心CSCD

马方综合征是一种常染色体显性遗传的多系统结缔组织疾病,主要由FBN1基因突变所致,临床表现不一,新生儿马方综合征尤其罕见,病情重,预后差。目前,尚无针对马方综合征的根治方法,早发现、早诊断、早治疗可有效延长患者的生存年限。该文就马方综合征的诊疗进展作一综述。     

胆道闭锁的诊断及治疗新进展

胆道闭锁的诊断基于临床表现、筛查及相关化验检查。近年来血液标志物的研发和超声检查手段的提高使得胆道闭锁的就诊年龄普遍提前,其中最具代表性的突破为血清基质金属蛋白酶-7,以其高灵敏度和特异度超越了现有血生化指标的诊断效能,并正在向临床推广应用;肝弹性成像技术在诊断及预后判断方面也能在很大程度上提高诊断效能。手术仍是治疗胆道闭锁的唯一方法,当前序贯手术治疗方案首先是Kasai肝门空肠吻合术,加以抗感染、减轻炎症等药物治疗方案,而Kasai手术失败及肝功能丧失的患者,最终需要肝移植挽救生命。因此胆道闭锁目前的研究重点内容为早期诊断标志物,以及特异性靶向性、防止进行性肝纤维化药物的研发。该文将综述目前胆道闭锁的诊断方法和治疗措施,并探讨潜在的研究方向。 ［中国当代儿科杂志,2022,24（11）：1269-1274］     

Rapid regression of lymphadenopathy upon rapamycin treatment in a child with autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of the immune system caused by inadequate induction of apoptosis via the Fas pathway, mainly characterized by generalized lymphadenopathy, splenomegaly, and autoimmune cytopenias, as well as increased risk of lymphoma. Although the clinical course of ALPS is highly variable, without treatment long‐term prognosis is unsatisfactory for most patients. ALPS has been treated with most of the existing immunosuppressive agents, with variable success. We hereby present a case of a child with ALPS whose greatly enlarged lymph nodes rapidly regressed upon initiation of rapamycin, a novel potential therapeutic agent in the treatment of ALPS. Pediatr Blood Cancer 2009;53:1117–1119. © 2009 Wiley‐Liss, Inc.     

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目的报道1例自身免疫性淋巴细胞增殖综合征的临床特点、诊断、治疗及随访,提高国内儿科医生对该病的认识。方法 2009年5月中山大学附属第一医院收治1例自身免疫性淋巴细胞增殖综合征患儿,回顾分析该患儿临床资料及诊疗过程,复习国内外相关文献。结果患儿1岁11个月,以全血细胞减少、肝脾淋巴结肿大为主要临床表现,并有肾小球肾炎、炎症性肠病的临床表现,CD3+且CD4、CD8双阴性细胞比例明显升高,伴PaIgG、ANA、ANCA、胰岛素自身抗体等抗体阳性。Fas、FasL及Casp10基因检测未发现基因突变。糖皮质激素联合其他免疫抑制剂治疗短期效果明显,但激素减量时易反复。结论本病例在临床上诊断自身免疫性淋巴增殖综合征可成立。提高对本病的认识可以减少误诊率。     

Splenectomy in two children with autoimmune lymphoproliferative syndrome and massive splenomegaly

Treatment of patients with ALPS has varied but presently there is no consensus about the optimal therapy. Splenectomy is an option but data regarding the postsplenectomy outcome in pediatric ALPS patients remain very limited. We present two children who suffered from anemia and physical discomfort from the large spleen. Both patients underwent uneventful splenectomy and experienced significant improvement in cytopenia, daily activity and well‐being. Furthermore the youngest patient showed a significant catch‐up growth. We conclude that in selected patients with marked splenomegaly and ALPS, splenectomy may be considered a treatment option. Pediatr Blood Cancer 2009;53:1124–1126. © 2009 Wiley‐Liss, Inc.     

X-连锁淋巴组织增殖综合征的临床表型和诊断

X-连锁淋巴组织增殖综合征(XLP)是一种少见的、常常是致死性的原发性免疫缺陷病,可由EB病毒感染诱发,表现为爆发性传染性单核细胞增多症、丙种球蛋白异常血症和淋巴增殖性疾病以及淋巴瘤.本病主要由编码淋巴信号活化分子相关蛋白(SAP)、X-连锁凋亡抑制因子(XIAP)和IL-2诱导的T细胞激酶(ITK)基因的突变引起.基因序列分析是确诊XLP的依据;SAP、XIAP、ITK蛋白的表达也可以作为筛查XLP的手段.家族史是需要考虑的主要客观指标,其他诊断标准包括患儿的临床表现、EB病毒感染后的EBNA抗体检测等.     

Response to steroid therapy in autism secondary to autoimmune lymphoproliferative syndrome

We report a child who developed autoimmune lymphoproliferative syndrome (ALPS) secondary to a heterozygous dominant negative mutation in the death domain of the Fas receptor. Previously developmentally normal, he had symptoms of autism with rapid regression in developmental milestones coincident with the onset of lymphoproliferation and autoimmune hemolytic anemia. Low-dose steroid therapy induced early and complete remission in the ALPS phenotype. There was subjective improvement, followed by objective improvement in speech and developmental milestones. We propose that autism may be part of the autoimmune disease spectrum of ALPS in this child, and this case represents a novel manifestation and target organ involvement in this disease.     

Mycophenolate mofetil as an alternate immunosuppressor for autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder due to a genetic defect concerning programmed cell death (apoptosis). Most patients are carriers of a heterozygous mutation affecting the TNFRSF6 (Fas). Treatment of autoimmune complications of ALPS includes corticosteroids, gamma-globulin infusions, and in refractory cases, splenectomy, cytostatic agents, and bone marrow transplantation. A 10-year-old boy with ALPS manifested by recurrent febrile episodes, lymphadenopathy, splenomegaly, and cytopenias refractory to corticosteroid therapy is presented. Treatment with mycophenolate mofetil, an immunosuppressive agent typically used in organ transplantation was initiated. This treatment was successful with resolution of thrombocytopenia, decrease in lymphadenopathy, and improvement of his general clinical condition for over 2 years of duration.     

Post-transplantation lymphoproliferative disorders: advances in diagnosis, prevention and management in children

With improving operative and postoperative survival after pediatric thoracic transplantation, attention has appropriately begun to focus on complications of long-term immunosuppression. One important complication is post-transplantation lymphoproliferative disorders. Much has been learnt about this spectrum of disorders over the last 15 years, including the pivotal role of primary Epstein-Barr virus infection in the etiology of most cases. Despite these advances, nomenclature remains confusing for the clinician, prediction of outcome is imprecise and treatment strategies are poorly defined. Indeed, no treatments have been subjected to comparative prospective clinical trials. Only recently has attention focussed on strategies for prevention. This article will review the current state of knowledge of post-transplantation lymphoproliferative disorders, with emphasis on recent advances in diagnosis, prevention and management.     

Deficiency of ADA2 mimicking autoimmune lymphoproliferative syndrome in the absence of livedo reticularis and vasculitis

Adenosine deaminase‐2 (ADA2) deficiency (DADA2) is associated with early onset polyarteritis nodosa and vasculopathy. Classic presentation includes livedo reticularis, vasculitis, and stroke. However, the phenotype and disease severity are variable. We present a 5‐year‐old female who presented with features that mimicked autoimmune lymphoproliferative syndrome (ALPS) in the absence of classic features of DADA2. Exome sequencing identified a novel homozygous splicing variant in ADA2 c.882‐2A > G. Patient responded to anti‐ tumor necrosis factor medication and is in complete remission. Hematologists should be aware of various hematological presentations of DADA2, including ALPS‐like disorder, that might lack vasculitis and livedo reticularis to prevent delay in initiating optimal therapy.     

Recent advances in prenatal diagnosis and treatment

This article is a summary of the prenatal and perinatal management of a variety of congenital lesions as practiced by the fetal treatment program at the University of California in San Francisco. Emphasis is placed on those lesions that are amenable to fetal intervention.     

Kallmann综合征研究进展及儿科早期诊断

单纯性低促性腺激素性腺发育不良合并嗅觉障碍是Kallmann综合征（KS）的主要临床特征,其主要病理机制涉及不同基因缺陷（如KAL1、FGFR1、PROK2/PROKR2等）,导致下丘脑促性腺激素释放激素（GnRH）合成分泌障碍。根据遗传模式KS可分为X连锁、常染色体显性和隐性遗传。应重视儿科阶段KS的早期诊断,进一步探索小儿阶段的有效治疗策略。     

庞贝病诊断与治疗的研究进展

庞贝病（Pompe disease）又称Ⅱ型糖原贮积症,是一种由于缺乏酸性α-葡糖苷酶（GAA）引起糖原在溶酶体内贮积的罕见常染色体隐性遗传疾病,尤以骨骼肌、心肌和平滑肌受累最为严重。患者表现为呼吸困难和运动障碍,伴或不伴有肥厚性心肌病。GAA基因突变具有种族和地域差异,随着研究的进展人们不断发现新的突变位点。庞贝病诊断的金标准是基因分析,传统方法如皮肤肌肉活检与干血斑样本检测对其诊断具有局限性。近年出现的产前诊断与新生儿筛查对其早期诊断具有重要意义。酶替代治疗（ERT）的效果令人满意,但可能引起免疫不耐受。新兴的靶向基因治疗、改进的ERT治疗有望在未来投入应用。该文就目前庞贝病的诊断和治疗的研究进展做一综述。     

儿童结核病的诊治进展

结核病是一种严重危害人类健康的慢性传染性疾病,临床表现不典型,尚缺乏灵敏度较高的有效检查手段,临床诊断难度较大。由于多重耐药性结核菌株（MDR-TB）的产生及儿童用药的局限性,以致儿童结核病的治疗愈加困难。该文就儿童结核杆菌感染的流行病学史、临床表现、结核菌素皮肤试验、影像学检查、实验室检查等与结核病诊断有关的研究进展以及治疗措施在近些年的发展做一综述。