Iron refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by mutations in the TMPRSS6 gene, which impairs iron homeostasis. We report a 4-year-old girl presented with a one-year history of IDA. Hemoglobin, transferrin saturation, and hepcidin levels were 6.5 g/dL, 1.6%, and 112.17 ng/mL, respectively. High-dose oral iron therapy partially corrected hemoglobin levels, and they declined after decreasing or stopping iron therapy. Genetic analysis of the TMPRSS6 gene identified compound heterozygotes of two novel pathogenic variants of c.811C>T in exon 7 (p.R271X) and c.1254C>G in exon 11 (p.Y418X). Her parents carried a heterozygous mutation of each variant.

Wiskott-Aldrich syndrome (WAS)/X-linked thrombocytopenia (XLT) is a rare X-linked disease characterized by thrombocytopenia, eczema, and recurrent infection. In addition, WAS/XLT increases incidence of autoimmune diseases and malignancies. We reported 7 male patients, 2 with WAS and 5 with XLT, from 6 different families. Two novel mutations, p.Gly387GlufsTer58 and p.Ala134Asp, were identified in patients with WAS. Both patients had severe clinical phenotypes compatible with classic WAS and developed lethal outcomes with intracranial hemorrhage. Other than that, one patient with XLT developed pineoblastoma.

A 12-year-old severe hemophilia boy had developed inhibitor since he was two. At 10 years of age, he received high dose factor VIII after plasma exchange in addition to bypassing agents for treatment of CNS bleeding, causing peak inhibitor titer of 3,360 BU. ITI was initiated when his inhibitor was decreased to 140 BU, and the prophylactic emicizumab had been added since the second year of ITI. After 3.5 years of ITI and emicizumab, his inhibitor titer was down to 0.56 BU (factor VIII recovery was 60% and half-life 5.5 hours). His QoL was remarkedly improved and without bleeding.

Background: Hemoglobin H (HbH) is usually recognized as mild thalassemia. However, a wide range of clinical manifestations, from fatal hydrops fetalis to asymptomatic mild anemia, is observed. A severity scoring system to guide the management of patients with HbH is needed. Objective: To develop a scoring system to predict the necessity of regular transfusion among patients with HbH. Methods: Patients were classified into 2 groups according to transfusion requirement: severe among transfusion-dependent thalassemia (TDT) and nonsevere among nontransfusion-dependent thalassemia (NTDT). Clinical and hematological parameters associated with transfusion dependency were identified and β-coefficients of significant parameters from multiple logistic regression analysis were used to develop a scoring system. Results: A total of 247 pediatric patients (24 severe, 223 nonsevere) with a median age of 14.3 (IQR 9.9-18.4) years were included. Multiple logistic regression analysis revealed 3 significant parameters associated with regular transfusion requirement including 1) age at diagnosis <2 years, 2) spleen size ≥3 cm and 3) Hb at steady-state <8 g/dL. Coefficients of the respective parameters were used to define the scores as 1, 2 and 2, respectively. A total score of ≥3 was associated with regular transfusion requirement among severe HbH (sensitivity 88%, specificity 83%). The newly developed scoring system was validated in the second cohort of 134 pediatric patients with HbH treated at another center. The cut-off score ≥3 yielded comparable sensitivity and specificity for the prediction.

MYH9 disorder is characterized by macrothrombocytopenia with or without granulocyte DÖhle body-like inclusion bodies. Diagnosis is made by immunofluorescence analysis and genetic study of the MYH9 gene. Our collaborative study between Thailand and Japan began with 67 Thai patients with macrothrombocytopenia. Of these, 11 patients(16.4%), aged 4 months-22 years with platelet counts ranging from 2,000-99,000/uL were diagnosed with MYH9 disorder. MYH9 gene mutations occurred in exons 1,16,30,38,40. One novel mutation was identified (c.4338T>C, p.F1446A). The results indicate that patients with macrothrombocytopenia should be tested for MYH9 disorder in order to avoid misdiagnosis to the other diseases, such as chronic immune thrombocytopenia.