A New Homozygous Mutation (c.393-394del TA/c.393-394del TA) in the NT5C3 Gene Associated With Pyrimidine-5'-Nucleotidase Deficiency: A Case Report.

Pyrimidine-5-nucleotidase (P5'N-1) deficiency is a rare nonspherocytic hemolytic anemia due to pyrimidine nucleotide deposition within erythrocytes. This rare erythrocyte disorder shows autosomal recessive inheritance with mutation of the pyrimidine-5'-nucleotidase gene, which is localized on 7p15-p14. Consanguinity of parents increases the probability of disease with novel mutations. Here, we report a 12-year-old boy with a delayed diagnosis of P5'N deficiency whose parents were consanguineous. He had a hemoglobin level of 7.5 g/dL, mean corpuscular volume of 93 fL, 7% reticulocyte, and lactate dehydrogenase of 678 IU/L. A peripheral blood smear showed polychromasia, marked anisopoikilocytosis with schistocytes, elliptocytes, stomatocytes, spherocytes, dacryocyte, and basophilic stippling in red blood. Decreased purine/pyrimidine ratio was 1.07 (normal range=1.4 to 2.98). Molecular analysis with direct DNA sequencing of the NT5C3 gene, codifying for P5'N-1, revealed the presence of a novel homozygous mutation, c393-394delTA, in the gene coding P5'N enzyme in the patient. To our knowledge, this is a newly defined mutation in P5'N deficiency.

Aplastic Anemia as an Immune-mediated Complication of Thymoma: A Case Report.

Thymomas are the most common masses located in the anterior mediastinum, and they are often associated with autoimmune disorders including myasthenia gravis, polymyositis, and aplastic anemia (AA). Autoreactive T-cell clones generated by the thymoma may lead to autoimmune disorders. We report the case of a 14-year-old boy who was examined for AA, and the underlying cause was determined to be an immune-mediated complication of thymoma. He had no matched sibling donors. He underwent thymectomy, and 3 months later he was treated with immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A. The duration of the IST was determined to be a period of 12 months. He has recently been in complete response condition for 6 months since IST stopped. IST is a successful treatment choice for thymomas associated with AA in childhood.

Chronic Neutropenia in Childhood: Experience From a Single Center.

Chronic neutropenia (CN) is defined as neutropenia that persists for >3 months; it is caused by a heterogeneous group of diseases in children. The aim of the present study was to evaluate the significance and clinical manifestations of CN in children at a single children's hospital. Between October 2004 and April 2014, CN patient data were evaluated retrospectively. Thirty-one patients were assessed in this study. Thirteen of them (41.9%) were younger than 12 months of age at initial diagnosis. There was no difference in the absolute number of neutrophils at diagnosis between the children aged younger than 12 months and those aged 12 months and older at CN onset. Twenty-two of the patients (70.9%) were diagnosed during treatment for acute infections. A total of 11 patients (35.5%) were hospitalized because of recurrent infections. Most of the recurrent infections occurred in the lungs (81.8%). Congenital neutropenia (CoN) was identified in 14 patients (45.1%). Eight of 14 patients (57.1%) required granulocyte-colony stimulating factor treatment, and none of them experienced adverse effects from this treatment. Fifteen patients (48.3%) were diagnosed with idiopathic neutropenia. Comparison between the idiopathic and CoN groups revealed no differences in age, the absolute number of neutrophils, or the presence of infection at diagnosis; however, differences were detected in sex and the rate of spontaneous recovery from neutropenia. Ten of the patients (32.2%) experienced spontaneous recovery from neutropenia during a follow-up period of 7 to 52 months. In current study, we found a higher CoN ratio in the CN patients compared with previous reports, which may be due to the high rate of consanguineous marriages in our country. However, the finding of CN requires several laboratory investigations, prolonged follow-up, and advanced molecular analysis, and its etiology can remain idiopathic.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

Torticollis in a haemophilic infant with inhibitor: a case of spinal epidural haematoma.

Central nervous system bleeding, which can be a life-threatening complication, is seen in 2.7% of patients with haemophilia. Spinal epidural haematomas represent about one-tenth of such cases. Here, we report on a 10-month-old boy with severe haemophilia A, who presented with torticollis. Although administration of factor VIII at a dose of 50 U/kg, the patient developed flaccid paralysis of the upper extremities. Factor VIII inhibitor screen was positive. Magnetic resonance imaging of the spine revealed spinal epidural haematomas, extending from C-1 to the cauda equina. Treatment was continued with recombinant activated factor VIIa without surgery. After 1 month, complete neurological recovery was achieved and fully resolved haematomas were detected on spinal MRI. A prompt radiological evaluation of the cervical spine with MRI should be made in patients with haemophilia presenting with torticollis. In addition, in the case of life-threatening bleeding in patients with haemophilia, the possibility of an inhibitor should be kept in mind.