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1.
J Pediatr ; 155(6): 829-33, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19628217

ABSTRACT

OBJECTIVE: To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID). STUDY DESIGN: Real-time PCR based quantification of TRECs for 471 healthy control patients and 18 patients with SCID with various genetic abnormalities (IL2RG, JAK3, ADA, LIG4, RAG1) were performed, including patients with maternal T-cell engraftment (n = 4) and leaky T cells (n = 3). RESULTS: TRECs were detectable in all normal neonatal Guthrie cards (n = 326) at the levels of 10(4) to 10(5) copies/microg DNA. In contrast, TRECs were extremely low in all neonatal Guthrie cards (n = 15) and peripheral blood (n = 14) from patients with SCID, including those with maternal T-cell engraftment or leaky T cells with hypomorphic RAG1 mutations or LIG4 deficiency. There were no false-positive or negative results in this study. CONCLUSION: TRECs quantification can be used as a neonatal mass screening for patients with SCID.


Subject(s)
DNA Repair/genetics , Neonatal Screening/methods , Receptors, Antigen, T-Cell/genetics , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/genetics , Adolescent , Adult , Child , Child, Preschool , Feasibility Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Predictive Value of Tests , Reverse Transcriptase Polymerase Chain Reaction , Ribonuclease P/blood , Severe Combined Immunodeficiency/blood , Young Adult
3.
Int J Hematol ; 87(1): 75-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18224417

ABSTRACT

We report a 1-year-old girl with Evans syndrome coexisting with histologically confirmed Langerhans cell histiocytosis (LCH) affecting the cervical lymph nodes, liver, and spleen. Anti-cardiolipin antibody, anti-SS-A antibody, and anti-SS-B antibody as well as a direct antiglobulin test and platelet-associated IgG were all positive at the onset, and these autoantibodies became negative with the resolution of LCH by chemotherapy. Serum T-helper-2 (Th2) cytokine levels such as those of interleukin (IL)-6 and IL-10 were high whereas those of Th1 cytokines such as IL-2 and interferon-gamma were low at the onset, and this cytokine imbalance was normalized during the resolution of LCH. These results suggest that cytokine imbalance due to LCH led to multiple autoimmune phenomena in the present patient.


Subject(s)
Anemia, Hemolytic, Autoimmune/complications , Antineoplastic Combined Chemotherapy Protocols , Histiocytosis, Langerhans-Cell/complications , Anemia, Hemolytic, Autoimmune/drug therapy , Cytarabine/administration & dosage , Cytokines/drug effects , Cytokines/metabolism , Female , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/pathology , Humans , Infant , Prednisolone/administration & dosage , Remission Induction , Syndrome , Vincristine/administration & dosage
4.
Haematologica ; 92(12): 1727-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18056008

ABSTRACT

We report a CD40 ligand deficiency (CD40LD) patient who was successfully treated with unrelated cord blood transplantation (URCBT). Conditioning regimen was busulfan and cyclophosphamide. The clinical course was uneventful and durable engraftment was achieved. This successful case encourages the use of URCB as an alternative donor source for CD40LD patients.


Subject(s)
Agammaglobulinemia/therapy , CD40 Antigens/deficiency , Cord Blood Stem Cell Transplantation , Genetic Diseases, Inborn/therapy , Living Donors , Neutropenia/therapy , Transplantation Conditioning , Agammaglobulinemia/genetics , Busulfan/administration & dosage , Cyclophosphamide/administration & dosage , Genetic Diseases, Inborn/genetics , Graft Survival , Humans , Infant , Male , Neutropenia/genetics
5.
J Pediatr Hematol Oncol ; 27(9): 495-8, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16189444

ABSTRACT

Malignant infantile osteopetrosis (MIOP) is a lethal disorder caused by osteoclast dysfunction. The only curative therapy for MIOP is stem cell transplantation (SCT). Because the number of patients is limited, the conditioning regimen and the use of alternative donors for SCT have been controversial and not established. The authors report a case of successful cord blood transplantation (CBT) with a nonmyeloablative regimen (NMR) for MIOP. The patient was a 9-month-old girl with MIOP. Before this diagnosis, she had received chemotherapy under the tentative diagnosis of juvenile myelomonocytic leukemia. She was on mechanical ventilation with tracheotomy due to the progression of MIOP when CBT with NMR was undergone. The conditioning regimen included fludarabine, melphalan, and antithymocyte globulin. Cyclosporine A and methylprednisolone were used for prophylaxis for graft-versus-host disease. Neutrophil engraftment was achieved on day 26 after SCT and has been fully maintained up to the present. Although grade 3 graft-versus-host disease and hepatic veno-occlusive disease occurred, both were controllable. Although the pretransplant condition of our patient was somewhat unusual, this is the first reported case of successful CBT with NMR for MIOP. Because of the urgent need, CBT can be considered as one of the SCT sources for MIOP, especially in a severe, life-threatening setting.


Subject(s)
Bone Neoplasms/therapy , Cord Blood Stem Cell Transplantation , Osteopetrosis/therapy , Transplantation Conditioning , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/pathology , Female , Humans , Infant , Osteoclasts/pathology , Osteopetrosis/diagnostic imaging , Osteopetrosis/pathology , Radionuclide Imaging
6.
Blood ; 103(4): 1305-10, 2004 Feb 15.
Article in English | MEDLINE | ID: mdl-14563640

ABSTRACT

We report here 7 new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS13. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants.


Subject(s)
Alternative Splicing , Anemia, Hemolytic/genetics , Metalloendopeptidases/genetics , Mutation, Missense , Thrombocytopenia/genetics , ADAM Proteins , ADAMTS13 Protein , Adult , Exons , Family Health , Female , Gene Expression , Humans , Infant, Newborn , Introns , Japan , Jaundice, Neonatal/genetics , Male , Metalloendopeptidases/chemistry , Pedigree , Protein Structure, Tertiary , Thrombospondin 1/chemistry
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