Language：Japanese   Publisher：Frontiers in Immunology  

Background: Newborn screening (NBS) for severe combined immunodeficiency (SCID) has improved the prognosis of SCID. In Japan, NBS testing (measurement of the T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC)) was launched in 2017 and has expanded nationwide in recent years. In this study, we report a Japanese patient with X-linked SCID with a novel IL2RG variant identified through NBS. The patient underwent cord blood transplantation (CBT). Case: The patient had no siblings or family history of inborn errors of immunity. He was born at 38 weeks of gestation and weighed 3,072 g. His NBS results revealed TREC 0 copies/10⁵ cells (normal value: >565 copies/10⁵ cells), which was considered suggestive of SCID. The patient was referred to our hospital. Although his lymphocyte count was 1,402/μL, naïve T cells and CD56⁺ natural killer (NK) cells were decreased to 0% and 0.05% of the total lymphocytes, respectively. Flow cytometric measurement testing revealed a decrease in γc protein expression in the B lymphocytes and NK lymphocytes. We identified a hemizygous novel missense variant (c.256A>C, p.Thr86Pro) of IL2RG. Both in silico and structural analyses revealed that this variant is likely pathogenic. At 3 months of age, he underwent CBT from a human leukocyte antigen-full-matched unrelated donor. The conditioning regimen included fludarabine (180 mg/m²) and targeted busulfan (35 mg×h/L). The patient achieved high-level donor chimerism and immune reconstitution, including B-cell function, at 13 months. Conclusion: Using NBS, the patient was diagnosed as having X-linked SCID with a novel missense variant of IL2RG. Early diagnosis using NBS tests enables safe hematopoietic stem cell transplantation without complications such as infection. We also found that even SCID with novel variants can be accurately diagnosed using the NBS program. In Japan, the test uptake rate is approximately 80% due to the high number of self-funded screening tests, and it is hoped that the uptake rate will increase in the future.

DOI： 10.3389/fimmu.2024.1478411

Scopus

PubMed

Language：Japanese   Publisher：Journal of Pediatric Hematology Oncology  

Herein, we describe a 14-year-old female patient with B-cell precursor acute lymphoblastic leukemia who relapsed in early consolidation. Minimal residual disease-negative complete remission was obtained after 1 cycle of inotuzumab ozogamicin therapy. She underwent HLA-haploidentical peripheral blood stem cell transplantation after a myeloablative conditioning regimen. Posttransplant cyclophosphamide, tacrolimus, and mycophenolate mofetil were administered for the prophylaxis of graft-versus-host disease. At 23 months, she was in complete remission. Although the administration of inotuzumab ozogamicin followed by haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide has been limited in children, this strategy may be an effective treatment for pediatric refractory acute lymphoblastic leukemia.

DOI： 10.1097/MPH.0000000000002079

Scopus

PubMed

Language：Japanese   Publisher：The Japanese Society of Pediatric Hematology / Oncology  

<p>A 2-year-old female presented with acute heart failure and renal failure, and she was started on Extra-corporeal membrane oxygenation (ECMO) and continuous hemodiafiltration (CHDF). ECMO led to improvement in her heart function; however, she developed high blood pressure following ECMO withdrawal. Computed tomography revealed a left adrenal tumor and double renal arteries that were narrowed at their origin. Urinary vanillylmandelic acid and homovanillic acid, as well as serum neuron-specific enolase levels were increased, and I¹²³-metaiodobenzylguanidine (I¹²³-MIBG) scintigraphy revealed I¹²³-MIBG accumulation in the tumor. Blood tests showed high plasma renin and aldosterone levels. Bone marrow aspiration revealed abnormal cells, and she was diagnosed as having neuroblastoma and renovascular hypertension. We concluded that a neuroblastoma concomitant with renovascular hypertension precipitated hypertensive cardiac shock and severe renal failure. Chemotherapy improved hypertension and renal failure. Chemotherapy with ECMO and CHDF are effective rescue strategies in patients with neuroblastoma complicated by severe heart and renal failure.</p>

DOI： 10.11412/jspho.58.166

CiNii Research

Language：Japanese   Publisher：The Japanese Society of Hematology  

<p>Herein, we describe a 13-year-old male adolescent who had chronic thrombocytopenia since infancy. In this case, X-linked thrombocytopenia (XLT) was suspected owing to a family history of chronic thrombocytopenia and small-sized platelets. Moreover, the patient was refractory to immunoglobulin therapy. The Wiskott-Aldrich syndrome protein (WASP) expression analysis revealed a decreased expression. Results showed a missense mutation [c.296A>G (p.Gln99Arg)] in exon 3 of the WASP-interacting protein region. Therefore, a diagnosis of XLT was made. To lift exercise restrictions, we initiated treatment with eltrombopag at a dose of 12.5 mg/day. The platelet count of the patient increased to approximately 50×10³/µ<i>l</i> after the treatment dose was escalated to 25 mg/day, and bleeding symptoms decreased after the patient resumed exercise. Ultrastructural platelet abnormalities and abnormal platelet aggregation were observed on transmission electron microscopy after the administration of eltrombopag. Therefore, eltrombopag treatment can increase platelet count and reduce bleeding symptoms in patients with XLT.</p>

DOI： 10.11406/rinketsu.62.257

PubMed

CiNii Research

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