Fanconi anemia gene mutations are not involved in sporadic Wilms tumor

Bi‐allelic germline mutations of the Fanconi anemia (FA) genes, PALB2/FANCN and BRCA2/FANCD1, have been reported in a few Wilms tumor (WT) patients with an atypical FA phenotype. Therefore, we screened a random cohort of 47 Dutch WT cases for germline mutations in these two FA‐genes by DNA sequencing and Multiplex Ligation‐dependent Probe Amplification (MLPA). Although several cases appeared to carry missense variants, no bi‐allelic pathogenic mutations were identified, indicating that bi‐allelic mutations in these FA‐genes do not contribute significantly to the occurrence of WT. Pediatr Blood Cancer. 2010;55:742–744. © 2010 Wiley‐Liss, Inc.     

Hepatic tumours during androgen therapy in Fanconi anaemia

The occurrence of liver tumours in the course of Fanconi anaemia (FA) has been well documented. We present a case, review the literature and conclude that androgen therapy would increase the risk of developing tumours, most of which appear to be benign (adenomas or peliosis) and androgen-dependent, generally decreasing in size after cessation of treatment. Survival of patients is poor, mostly because of the rapid evolution of untreated FA, rather than rupture or degencration of the tumour. In the absence of an allogenic bone marrow transplantation, administration of haematopoietic growth factors might be effective. As a preventive measure, other types of unsubstituted androgens may be used.     

Iron therapy resistant microcytic anaemia in a 13-year-old girl with Castleman disease

We describe the case history of a 13-year-old girl with chronic fatigue and prolonged microcytic anaemia. She received oral iron since the age of 11 but failed to respond to it. Laboratory studies revealed elevated C-reactive protein and hypergammaglobulinaemia. A large solitary mesenterial lymph node could be demonstrated by ultrasonography and CT. A diagnosis of Castleman disease was suspected and confirmed histologically. After surgical removal of the lymphoma the patient recovered completely. Conclusion Castleman disease should be considered in cases of chronic fatigue, unexplained fever, microcytic anaemia and hypergammaglobulinaemia. Received: 10 February 1996 Accepted: 23 March 1996     

Fulminant limb and retroperitoneal necrotizing fasciitis in a 15-year-old girl with Fanconi anaemia

Necrotizing fasciitis (NF) is an uncommon soft-tissue infection in children that carries a high mortality rate. We present a 15-year-old girl with chronic pancytopenia secondary to Fanconi anaemia who developed extensive NF of the lower limb, which unfortunately resulted in a fatal outcome. Immunodeficiency is a known risk factor for the development of this condition. The findings in this case demonstrate that patients with Fanconi anaemia may be susceptible to NF and that the clinical course may be more aggressive due to underlying immunosuppression. Prompt diagnosis of NF is vital in order to initiate appropriate treatment and to optimize patient outcome. Radiological investigation demonstrated extensive soft-tissue gas and destruction affecting the entire lower limb, abdominal wall and retroperitoneum, which led to timely definitive diagnosis and management.     

Fulminant liver failure in a 12-year-old girl with sickle cell anaemia: Favourable outcome after exchange transfusions

Acute liver failure is unusual unusual in sickle cell anaemia. We describe a child with homozygous sickle cell anaemia who developed acute liver disease of abrupt onset during an episode of limb pain. She presented with sudden onset of persistent vomiting, headache, lethargy, epistaxis, and painful liver enlargement. Laboratory investigations were indicative of cholestasis and severe liver failure with profound prolonged clotting times, hypofibrinogenaemia, elevated serum ammonia and lactic acidosis. The symptoms were promptly and completely reversed by two partial exchange transfusions. No evidence of viral infection was found. Cholelithiasis was ruled out by ultrasonography. The child recovered from what appeared to be massive hepatic sickling with no apparent sequelae.Conclusion Massive hepatic sickling should be considered in the differential diagnosis of a child with homozygous sickle cell disease who suddenly develops acute liver failure. Exchange transfusion should be promptly carried out so as to reverse ischaemic hepatic injury.     

Fanconi anemia and biallelic BRCA2 mutation diagnosed in a young child with an embryonal CNS tumor

Medulloblastoma, the most common pediatric malignant brain tumor often arises sporadically; however, in a subgroup of patients, there exist familial conditions such as Fanconi anemia with biallelic BRCA2 mutation that predispose patients to developing medulloblastoma. Biallelic inactivation of BRCA2 in Fanconi anemia has been previously described in only 11 patients with medulloblastoma in the literature to date. Here we report two siblings diagnosed with central nervous system embryonal tumors at an early age in association with biallelic BRCA2 inactivation, including the first reported case of a spinal cord primitive neuroectodermal tumor (PNET) in a BRCA2/FANCD1 kindred. Pediatr Blood Cancer 2009;53:1140–1142. © 2009 Wiley‐Liss, Inc.     

In vitro CFU-E and BFU-E responses to androgen in bone marrow from children with primary hypoproliferative anaemia: a possible therapeutic assay

The effects of natural and synthetic androgens on erythroid colony formation in children's bone marrow cultures were studied using a methylcellulose microculture assay. In an attempt to predict the clinical response to androgens in two children with Fanconi anaemia (FA) and two children with Diamond-Blackfan syndrome (DB), we tested the hormonal stimulation of testosterone, nortestosterone and etiocholanolone on CFU-E, BFU-E and uroporphyrinogen I synthase activity (UROS). We observed that colony formation and UROS activity were reduced when compared to values obtained with normal children's bone marrow cultures. The addition of steroids to the cultures significantly enhanced the numbers of CFU-E and BFU-E derived colonies and their UROS activity in marrow from patients with FA and one patient with DB. The strong depletion of marrow progenitor cells in the unresponsive marrow from child 4 with DB could explain the absence of hormonal response. Whereas the responsiveness to steroids varied according to the individual, the in vitro testing of erythroid differentiation in the presence of androgens theoretically may lead to an effective prediction of response to therapy in children with hypoplastic anaemia.Abbreviations FA Fanconi anaemia - DB Diamond-Blackfan syndrome - BFU-E burst forming unit-erythroid - CFU-E colony forming unit-erythroid - UROS uroporphyrinogen I synthase - EPO erythropoietin     

Hashimoto thyroiditis,distal renal tubular acidosis,pernicious anaemia and encephalopathy: A rare combination of auto-immune disorders in a 12-year-old girl

A case of a 12-year-old girl with a multiple auto-immune disorder is reported. She showed Hashimoto thyroiditis which subsequently developed to hashitoxicosis and distal renal tubular acidosis at 5 years of age, pernicious anaemia at the age of 9 and severe encephalopathy at the age of 12. Laboratory studies revealed very high titres of anti-microsomal and anti-thyroglobulin antibodies and positive gastric parietal cell antibody. As to the encephalopathy, positive oligoclonal IgG bands and high values of IgG index and IgG synthesis ratio in CSF were observed with aggravation of her neurological symptoms. High-dose steroid therapy was effective toward the encephalopathy. Paediatricians should pay careful attention to patients with Hashimoto thyroiditis for association with other auto-immune disorders.     

Hepatocellular carcinoma associated with arteriohepatic dysplasia in a 4-year-old girl

Hepatocellular carcinoma and obliterated hepatic bile duct were found at postmortem examination in a 4-year-old girl with arteriohepatic dysplasia (Alagille's syndrome). AFP level was extremely high. Liver cirrhosis was present on percutaneous needle biopsy 9 months before she succumbed in progressive liver failure. Episodes of repeated gastrointestinal, life-threatening hemorrhages occurred during the last 6 months of her life. Histopathologic findings of the eyes were documented at autopsy.     

Haploidentical stem cell transplantation as a salvage therapy for cord blood engraftment failure in a patient with Fanconi anemia

A 7‐year‐old male with Fanconi Anemia who developed primary graft failure following one antigen‐mismatched unrelated cord blood transplantation and a nonradiation‐based conditioning, underwent a second hematopoietic stem cell transplantation (HSCT) from his 2‐loci mismatched haploidentical father, using a nonradiation‐based regimen, 79 days after the first HSCT. A sustained hematological engraftment was achieved at 9 days post‐second HSCT. At 15 months post‐second HSCT; the patient demonstrated normal blood counts, sustained donor chimerism, and no evidence of GVHD. Haploidentical HSCTs as primary or secondary sources of stem cells, with appropriate T‐cell depletion, may be a readily available option in the absence of HLA‐matched related or unrelated donors. Pediatr Blood Cancer. 2010;55:580–582. © 2010 Wiley‐Liss, Inc.     

Mutations of the Epstein-Barr virus LMP-1 oncogene in a 10-year-old Japanese girl with nasopharyngeal carcinoma

A 10-year-old patient with nasopharyngeal carcinoma (NPC) was studied for mutations within the carboxy-terminal portion of the Epstein-Barr virus (EBV) latent membrane protein (LMP)-1 gene. The EBV genome, defined as type A, was detected in biopsied tumor specimens by Southern hybridization with specific probes. Sequence analysis of the carboxy-terminal part of the LMP-1 gene revealed no deletions but seven single-base substitutions, four of which were found to be identical to those previously detected in codons for amino acids 322 to 366 in the Chinese NPC CAO. Although yet unresolved, the observed mutations may be associated with the pathogenesis of NPC.     

Dysplastic features,growth retardation,malrotation of the gut,and fatal ventricular septal defect in a 4-month-old girl with ring chromosome 15

A 20-day-old female neonate was admitted with symptoms caused by a large ventricular septal defect which was subsequently confirmed angiographically. Other clinical findings were pre-and postnatal growth retardation, microcephaly, dysmorphism of ears, fingers and feet. Cytogenetic analysis revealed a ring chromosome 15. Despite a palliative banding operation of the pulmonary artery, the infant succumbed to complications of her congenital heart disease in the 4th month of life.Abbreviations NOR nucleolar organizer regions     

连续性血液净化对多器官功能障碍幼猪T辅助细胞免疫功能影响的机制研究

目的 研究连续性血液净化(CBP)对多器官功能障碍(MODS)幼猪在疾病不同时期外周血Th1、Th2细胞数量及其细胞培养上清液中细胞因子(IFN-γ、TNF-α、IL-12,IL-10、IL-4)水平的影响.方法 24只幼猪随机分为对照组和CBP干预组,每组12只.内毒素诱导多器官功能障碍.CBP主要采用连续性静脉静脉血液透析滤过(continuous venovenous hemodiafiltration,CVVHDF).造模完成后为0 h,MODS对照组在造模后0、2、4、6 h进行检测;血液净化干预组造模后即开始CVVHDF,分别在0 h及CVVHDF干预2 h、4 h、6 h进行检测.在各时点采用免疫磁珠分离两组幼猪外周血T辅助细胞,采用流式细胞仪检测Th1、Th2细胞数目,ELISA检测各时点T细胞培养上清液中IFN-γ、TNF-α、IL-12、IL-10、IL-4的表达水平.结果 幼猪诱导MODS模型后,辅助性T细胞分泌炎症因子TNF-α明显上升,而促进Th1细胞分化的因子IL-12和Th1细胞因子IFN-γ和调节因子IL-10呈下降趋势,Th2细胞因子IL-4则没有明显的变化,Th1/Th2比值下降;经过CVVHDF治疗,TNF-α和IL-4减少,IL-12、IFN-γ和IL-10在CVVHDF6 h后明显上升,Th1/Th2比值上升.结论 MODS幼猪模型经过CVVHDF治疗,有助于炎症因子的清除,增加机体的细胞免疫功能,恢复Th1/Th2的平衡.     

Novel mutations in SH3TC2 in a young Japanese girl with Charcot‐Marie‐Tooth disease type 4C

Charcot‐Marie‐Tooth disease type 4C (CMT4C) is an autosomal recessive demyelinating form of CMT characterized clinically by early onset and severe spinal deformities, and is caused by mutations in SH3TC2. We describe the case of a 10‐year‐old Japanese girl diagnosed with CMT4C. The patient developed progressive foot deformities such as marked pes cavus and ankle contracture, with mild muscle weakness in both legs, and generalized areflexia. On electrophysiological studies, motor nerve conduction velocity ranged from 22.3 m/s in the tibial nerve to 48.2 m/s in the median nerve. Sensory nerve conduction velocity ranged from 30.3 m/s in the sural nerve to 52.8 m/s in the median nerve. Sequence analysis of candidate genes identified two novel heterozygous mutations, c.229C>T and c.2775G>A, in SH3TC2. The patient was diagnosed as having CMT4C with novel mutations, making this the first documented Japanese pediatric case.