Bone marrow transplantation in chronic granulomatous disease

A 5-month-old Amish infant boy with chronic granulomatous disease underwent bone marrow transplantation from his 5-year-old, histocompatible brother after a preconditioning regimen of busulfan 2 mg/kg/day for 4 days, followed by cyclophosphamide 50 mg/kg/day for 4 days. At the time of bone marrow transplantation, he was free of infection, and remained so throughout the course of the transplant. He was engrafted promptly, with complete reversal of the neutrophil function defect and no sign of graft-versus-host disease. This was followed by loss of the erythroid graft and deterioration in neutrophil function over a period of 9 months. Sixteen months after transplantation, he is free of infection and growing normally, with essentially no evidence for neutrophil engraftment.     

Bone marrow transplantation in chronic granulomatous disease

We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was with-out complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft.     

Allogeneic bone marrow transplantation with reduced intensity conditioning for chronic granulomatous disease complicated by invasive Aspergillus infection

Chronic granulomatous disease (CGD) is a rare disorder characterized by recurrent infections, often resulting in impaired quality of life and death. Allogeneic BMT provides a definitive cure for CGD, but carries a significant risk of mortality and morbidity. The risk is higher for those who have invasive fungal infection prior to transplant. Reduced intensity conditioning (RIC) is associated with less toxicity from the conditioning agents and may provide an alternative option for all non-malignant diseases. We report a case of successful allogeneic BMT after RIC for a case of X-linked CGD complicated by severe invasive aspergillosis (IA).     

Successful bone marrow transplantation in an 8-month-old patient with chronic granulomatous disease

An eight-month-old boy with chronic granulomatous disease (CGD) received HLA identical sibling bone marrow transplantation (BMT) following busulphan and cyclophosphamide conditioning. No graft-versus-host disease was demonstrated. Five years after transplantation, mixed chimerism was 60% in peripheral blood, and 85% of his neutrophils had normal oxidative burst activity. He is now six years old, in very good health and growing well. In this period, he experienced no severe infectious diseases. To our knowledge, this is the first case of CGD who had BMT in Turkey. His successful outcome illustrates that BMT in a patient with CGD in the first years of life should be considered early if an HLA-matched donor is already available, before development of any recurrent life-threatening infections or irreversible organ damage.     

Successful bone marrow transplantation in a pediatric patient with chronic myeloid leukemia from a HLA-identical sibling selected by preimplantation HLA testing

We report successful bone marrow transplantation in an 11-year-old male with chronic myeloid leukemia from his HLA-identical sibling selected by preimplantation HLA testing. Because collection of cord blood failed, the transplantation was performed when the donor reached the age of 19 months, and sufficient bone marrow could be harvested safely. The patient was BCR/ABL negative at the time of transplantation after complete molecular response to imatinib. Currently, 16 months post-transplantation he is well and in complete molecular remission. This report describes preimplantation HLA-genotyping to deliver a matched sibling donor for successful transplantation of a malignant disorder.     

Successful unrelated bone marrow transplantation in a child with chronic granulomatous disease complicated by pulmonary and cerebral granuloma formation

We report on a 6-year-old boy with chronic granulomatous disease (CGD) complicated by chronic inflammatory reactions with formation of large pulmonary granuloma as well as intracerebral lesions. Bone marrow transplantation (BMT) from an unrelated donor led to stable reconstitution, to rapid resolution of pulmonary granuloma, and to rapid resolution of intracerebral lesions.     

X连锁慢性肉芽肿病及其基因突变

慢性肉芽肿病(CGD)是一种少见的遗传性疾病,分为X连锁CGD(X-CGD)和常染色体隐性遗传CCD。还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶的膜结合成分即细胞色素b558分为α和β亚单位。X-CGD是编码β亚单位gp91-phox的基因突变所引起。X-CGD的基因突变常为大片段碱基对的缺失、小片段碱基对的缺失或插入、错义突变和无义突变等。目前已有300多种gp91-phox的基因突变被登记收入国际X-CGD数据库。该文着重介绍关于内含子及拼接位点的突变。     

Prenatal diagnosis and novel mutation in X-linked chronic granulomatous disease

BackgroundChronic Granulomatous Disease (CGD) is a rare primary immunodeficiency caused by the alteration of the enzyme complex NADPH oxidase, which affects the phagocytic function. CGD patients are susceptible to recurrent infections mainly caused by bacteria and/or fungi.MethodsWe studied a 6 year-old boy with suspicion of CGD. The diagnosis was confirmed based on the functional study of NADPH oxidase. Simultaneously, the second pregnancy of the mother was reported and genetic counselling was requested.ResultsWe identified a new disease-causing mutation by direct sequencing of the CYBB gene (X-linked CGD). The prenatal study resulted in the identification of the same mutation in the foetus.CommentsMolecular genetics characterisation of CGD is needed to obtain an accurate diagnosis of the disease and to offer prenatal diagnosis and genetic counselling in future pregnancies.     

Chronic granulomatous disease 100% corrected by displacement bone marrow transplantation from a volunteer unrelated donor

A boy whose chronic granulomatous disease (CGD) manifested in infancy, and whose elder brother had died at 7 years of age, had phagocytes with complete lack of functional cytochrome B-245 and which could not be induced by interferon gamma to achieve adequate staphylococcal killing. He underwent an elective displacement bone marrow transplant from a volunteer unrelated donor at the age of 8 months. This has achieved 100% replacement of the CGD granulocytes by those of the normal volunteer and the boy has since had a normal childhood for 3 years. Six previous transplants for CGD are briefly reviewed and illustrate that the host abnormal marrow must be completely displaced using an adequate dose of busulphan to ensure 100% stable engraftment of the donor's marrow and that this is best done under elective conditions before septic foci and irreversible organ damage have occurred. Criteria need to be developed to identify early those patients likely to have severe morbidity.     

新生儿X-连锁慢性肉芽肿病4例分析暨文献复习

目的了解X-连锁慢性肉芽肿病（X-CGD）患儿的临床特点、治疗方法及基因突变类型。方法选择我科2013年4-12月经基因检测明确诊断为X-CGD的病例,总结患儿起病时间、症状、影像学表现、病原学检查、治疗及转归情况,了解基因突变类型。结果研究期间共收治4例X-CGD患儿,均为男婴,起病日龄13~17天,诊断日龄24-34天,1例有家族史。首发症状发热3例,咳嗽1例。肺CT表现为结节、不规则、球形或类圆形高密度灶。痰培养1例为烟曲霉菌和金黄色葡萄球菌,1例为白色念珠菌,2例阴性;血培养均阴性;血清半乳甘露聚糖（GM）试验阳性3例。应用抗细菌联合抗真菌治疗2-3周,4例均好转出院,随访6个月3例未复发,1例出院后未按医嘱服药生后5个月因反复严重感染死亡。CYBB基因突变分析示缺失突变1例,插入突变1例,错义突变2例,患儿母亲均为携带者。结论本病在新生儿期呼吸道症状及体征相对较轻,但影像学显示肺部病变严重,肺CT表现为多发结节或团块影,常规体液和细胞免疫功能正常的新生儿应考虑X-CGD。CYBB基因突变分布广泛,异质性明显,基因突变分析将成为产前诊断的重要工具。     

重症卡介苗淋巴结炎与儿童X连锁慢性肉芽肿病

慢性肉芽肿病(chronic granulomatous disease,CGD)是少见的原发性吞噬细胞免疫缺陷病.患者的多形核粒细胞不能通过烟酰胺腺嘌呤二核苷磷酸(NADPH)氧化酶产生超氧阴离子(O2-)来有效杀灭入侵的微生物.患者在儿童早期易于发生反复致命的过氧化氢酶阳性细菌和真菌感染,在慢性炎症部位形成肉芽肿[1].     

二氢罗丹明流式细胞分析方法用于X-连锁慢性肉芽肿病诊断和携带者筛查

No abstract available

     

X- 连锁慢性肉芽肿病CYBB 基因突变分析及产前诊断

目的分析X连锁慢性肉芽肿病(X-CGD)的临床特征及CYBB基因突变。方法回顾分析1例X-CGD患儿的临床资料及其家系的CYBB基因检测结果。结果男性患儿,新生儿期起病,以反复严重的肺部感染为主要表现。患儿无刺激组及脂多糖(LPS)刺激组四唑氮蓝试验(NBT)均为0%,中性粒细胞氧化指数(NOI)为1.15。基因分析显示,患儿CYBB基因第6外显子出现缺失突变(579-582del ATTA),由此引起编码序列从189位异亮氨酸(I)发生移码突变,于212位氨基酸提前出现终止密码子(I 189 fs X 212)。患儿母亲及外祖母均为突变基因携带者。患儿母亲下一胎羊水细胞的CYBB基因未发现相同缺失突变。结论基因诊断1例CYBB基因突变X-CGD患者及其家系,产前基因检测可避免X-CGD患儿出生。     

Persistent developmental delay despite successful bone marrow transplantation for purine nucleoside phosphorylase deficiency

A 10-month-old girl with a history of recurrent candidiasis, developmental delay, and a fulminant varicella infection is described. The diagnosis of purine nucleoside phosphorylase (PNP) deficiency was suggested by a reduced level of serum uric acid and confirmed by measurement of PNP activity. A human leukocyte antigen-matched bone marrow transplantation resulted in immune reconstitution, but poor neurodevelopmental progression.     

Immunological reconstitution by allogeneic bone marrow transplantation in a child with the X-linked hyper-IgM syndrome

A successful transplantation of sibling marrow in a patient with the X-linked hyper-IgM syndrome is reported. Engraftment of HLA-identical marrow cells was obtained, although complicated by grade I acute graft-versus-host disease. Expression of the CD40 ligand (CD40L, CD154) by activated T-cells from the recipient remained at low levels until 10 months after the transplantation, but then normalized. The patient is now fully competent in immune function without any episodes of severe infection 24 months later. Conclusion Allogeneic bone marrow transplantation is a reasonable therapeutic option for X-linked hyper-IgM syndrome if HLA-matched family donors are available. Whether dysregulation of CD40L expression causes post-transplant immunological abnormalities remains to be clarified. Received: 25 May 1998 / Accepted in revised form: 17 July 1998     

Successful allogeneic unrelated bone marrow transplantation using reduced-intensity conditioning for the treatment of X-linked adrenoleukodystrophy in a one-yr-old boy

Abstract:  The childhood cerebral form of X-linked ALD is a demyelinating disorder of the central nervous system, which rapidly leads to total disability and death. Allogeneic stem cell transplantation benefits patients who show early evidence of the demyelination. We report here a one-yr-old boy with ALD who received HLA-matched unrelated BMT in an early stage of the disease after careful planning and observation since his birth. BMT was performed when MRI began to show slight signal intensity changes in the white matter of the brain. Pretransplant conditioning consisted of fludarabine, l -PAM and TBI (2 Gy). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. The patient showed an uneventful BMT course with fast and stable engraftment. Following BMT, the plasma levels of VLCFA decreased gradually and MRI changes improved. The patient did not have any evidence of further neurological deterioration 22 months following the transplant. Although this is still a short follow-up, it has been shown that BMT should be considered when a child has a biochemical diagnosis and MRI findings of ALD without any neurological signs. RIST should be considered as a pretransplant conditioning for ALD.