Kazuko Kudo

There are conflicting reports about the involvement of single nucleotide polymorphisms (SNPs) of the ataxia telangiectasia mutated (ATM) gene with cancer, and the consequences of these SNPs for ATM function remain unclear. We therefore sought to identify SNPs of the ATM gene in pediatric Hodgkin disease (HD) and to analyze ATM function in cells from patients with these SNPs. We have identified SNPs of the ATM gene in 5 of 14 children (S1455R, n = 1; H1380Y, n = 1; N1650S, n = 2; and I709I, n = 1). One patient had nonsense-associated altered splicing of the ATM gene. Lymphoblastoid cell lines expressing the S1455R and N1650S exhibited defective ATM-mediated p53 phosphorylation and Chk2 activation; cells expressing the H1380Y exhibited defective c-Abl activation after X-irradiation. Expression of the N1650S in ATM-null fibroblasts conferred only partial hyperradiosensitivity. Furthermore, the introduction of N1650S ATM into U2OS cells, which express wild-type ATM, showed reduced p53-Ser15 phosphorylation, suggesting a dominant-negative effect of the N1650S over the wild-type ATM protein. We conclude that the rare polymorphic variants of the ATM gene that we identified in children w

Human herpesvirus 6 (HHV-6) infection was studied in 82 bone marrow transplant (BMT) recipients (72 allogeneic, 10 autologous). All recipients and 30 donors were seropositive for HHV-6 antibody at the time of bone marrow transplantation. Thirty-one recipients (37.8%) had HHV-6 viremia 2-4 weeks after transplantation. The incidence of HHV-6 viremia was significantly higher among allogeneic BMT recipients than in autologous BMT recipients (P = .011). Therefore, the following analyses of allogeneic BMT recipients were carried out (n = 72). Geometric mean antibody titers (log10) were significantly higher in recipients without viremia than in those with viremia (1.84 ± 0.39 vs. 1.61 ± 0.42 P = .022). Logistic regression analysis demonstrated that leukemia or lymphoma is an independent risk factor (P = .031) for HHV-6 viremia. Rash occurring within 1 month after transplantation was observed in 17 (54.8%) of 31 recipients with HHV-6 viremia but in only 8 (19.5%) of 41 recipients without HHV-6 viremia (P = .001). © Oxford University Press 2002.

Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900×10⁹/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea.

An 8-month-old boy was admitted because of paleness. Laboratory studies disclosed microcytic and hypochromic anemia: red blood cell count 156×10⁴/μl, hemoglobin 3.5 g/dl, mean cell volume 66 fl, and reticulocytes 0.5 ‰. Serum iron was 433 μg/dl and exocrine pancreatic dysfunction was not observed. Examination of bone marrow revealed prominent erythroid hyperplasia; 18% of the erythroblasts were distinct ringed sideroblasts. Electron microscopic studies found intramitochondrial iron deposits in the erythroblasts. The patient was given a diagnosis of sideroblastic anemia and responded to oral pyridoxine (50 mg/day) with an immediate increase of reticulocytes to 97 ‰, resulting in an improved hemoglobin concentration. He has maintained remission for more than 1 year following discontinuation of pyridoxine, which was administered for 2 months.<br>Congenital sideroblastic anemia is relatively rare and mostly occurs in males, suggesting an X-linked recessive mode of inheritance. Recently, X-linked sideroblastic anemia has been shown to be caused by missense mutations in the δ-aminolevulinic acid synthase (ALAS) gene. A point mutation in exon 5 of the ALAS gene was found in this patient. Iron-deficiency anemia is the most common hematologic disease of infancy and childhood, resulting from lack of sufficient iron for synthesis of hemoglobin. It is therefore mandatory to differentiate sideroblastic anemia from iron-deficiency anemia and other common anemias.