Berna Atabay

MUTATION OF THE PROTON-COUPLED FOLATE TRANSPORTER GENE (PCFT-SLC46A1) IN TURKISH SIBLINGS WITH HEREDITARY FOLATE MALABSORPTION

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder characterized by systemic and central nervous system folate deficiency. Turkish siblings are reported with the clinical syndrome of HFM, homozygous for deletion of 2 bases (c.204_205 delCC) within the first exon of the proton-coupled folate transporter (PCFT) gene, causing a frameshift. Low blood and cerebrospinal fluid folate levels were detected at ages 3.5 and 1 month. Treatment with parenteral 5-formyltetrahydrofolate resulted in normal development now at ages 3 and 1 year. Extending current knowledge on the phenotypic manifestations of HFM and the PCFT mutation spectrum will provide opportunities to define possible genotype-phenotype correlations and clarify the basis for the phenotypic variability that is characteristic of this disorder.

Oral cyclic megadose methylprednisolone therapy for chronic immune thrombocytopenic purpura in childhood.

Abstract: The objectives of this study were to investigate the effectiveness of oral megadose methylprednisolone (OMMP) therapy in children with chronic immune thrombocytopenic purpura (ITP). Twenty‐two patients were given oral methylprednisolone daily for 7 d (30 mg/kg for 3 d and then 20 mg/kg for 4 d). OMMP therapy was repeated once per month if the platelet count was less than 20,000/mm3 at the 30th day of therapy, for up to six courses. The number of platelets of all patients increased gradually during the OMMP therapy, with a peak number at the 7th day, then decreased until the 14th day, and remained relatively stable until 12 months. During the study no patient had a platelet count less than 20,000/mm3 at the 3rd day and 50,000/mm3 at the 7th day. Although the number of platelets was gradually decreased between the 7th and 14th days, it remained above 100,000/mm3 for at least 12 months in the nine patients, and above 20,000/mm3 in the four patients. None of these 13 patients required hospitalization or therapy during the follow‐up period. All of the patients tolerated the medication well. None of them reported side‐effects that were severe enough to discontinue therapy. We conclude that OMMP therapy is a safe, easy and effective therapy in children with refractory chronic ITP, and it may provide long‐term remission in about two thirds of the patients.

Investigation of megakaryocyte apoptosis in children with acute and chronic idiopathic thrombocytopenic purpura.

Abstract: Objective: Although the platelet destruction shows a primary role in the thrombocytopenia of idiopathic thrombocytopenic purpura (ITP), it has been demonstrated that impaired platelet production may also contribute to the severity of thrombocytopenia in ITP. The present study examined megakaryocyte apoptosis in bone marrow aspirates of children with acute and chronic ITP and investigated the role of megakaryocyte apoptosis in ITP pathophysiology.

Autoimmune lymphoproliferative syndrome: report of two cases and review of the literature

Abstract. Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease occurring in childhood. Recently, it has been shown that heritable mutations in Fas or Fas ligand genes, which regulate lymphocyte survival by triggering apoptosis of lymphocytes, are the most frequent cause of ALPS. Patients with ALPS frequently have lymphadenopathy, splenomegaly and hepatomegaly, especially at young ages. A positive result of the Direct Coombs test, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura are the most common features of autoimmunity in patients with ALPS. Elevated numbers and percentages (>1%) of double-negative (CD4–CD8–) T cells, and characteristic pathologic findings in lymph nodes or spleen are other important diagnostic features. In this report, we present the clinical, immunologic, and pathologic features of two children who were diagnosed with ALPS. The early recognition of ALPS in children with enlarged lymph nodes, hepatosplenomegaly, and autoimmune hematologic features has important diagnostic and prognostic value in avoiding expensive and time-consuming studies and unnecessary treatments. The ratio of CD4–CD8– T cells, immunoglobulin levels and the histopathologic features of lymph nodes should be rapidly determined in these patients in order to establish an early diagnosis and treatment.

A pediatric case of lymphomatoid granulomatosis with onset after completion of chemotherapy for acute myeloid leukemia

In this case report, we present a pediatric case of lymphomatoid granulomatosis (LG) with onset just after the completion of chemotherapy for childhood acute myeloid leukemia (AML). After the completion of maintenance therapy, the patient was admitted to our clinic with a complaint of cough. Radiologic examinations revealed nodular lesions in lungs, liver, and kidney. His bone marrow was in remission. The histopathologic examination of the open lung biopsy was consistent with LG. He received only one cycle of cyclophosphamide and high-dose methyl prednisolone treatment and continued to receive interferon (IFN) alpha-2b therapy for 18 months. This treatment regimen resulted in an excellent response. In conclusion, LG may occur after the treatment of pediatric AML as a rare complication and IFN alpha-2b may be an effective treatment choice in these patients.

POLYCYTHEMIA VERA IN A 12-YEAR-OLD GIRL: A Case Report

A case of a 12-year-old girl presenting with headache and splenomegaly and fulfilling the diagnostic criteria of polycythemia vera is reported. Her peripheral blood values were as follows: hemoglobin 18 g/dL, red blood cells 7,000,000/mm 3 , white blood cells 22,000/mm 3 , and platelets 1,248,000/mm 3 . Phlebotomy was performed initially but was ineffective. Afterward 100 mg/kg per day aspirin and 30/mg/kg per day hydroxyurea were given. The patient has been asypmtomatic for 1 year and her recent hemoglobin level is 15.5 g/dL, platelet count 922,000/mm 3 , and white blood cell 12,800/mm 3 . Polycythemia vera is an extremely uncommon disease in childhood and for this reason its treatment is not well established.

Neutrophil Apoptosis in Patients with β-Thalassemia Major

Increased susceptibility to infection is reported in patients with g -thalassemia major due to toxic effect of iron on neutrophil functions and reticuloendothelial system dysfunction. This study investigated the association between the neutrophil apoptosis and frequency of infection episodes, desferrioxamine treatment, and serum ferritin levels in patients with g -thalassemia major. A total of 35 children diagnosed with g -thalassemia major were enrolled. Group 1 consisted patients who were receiving desferrioxamine (DFO) and group 2 consisted of patients who did not start to receive DFO. A total of 15 healthy children were enrolled to serve as a control group. Frequency of infection episodes within a year was noted from hospital records. In all patients, the same method based on flow cytometry (annexin V labeled with FITC) was used to assess neutrophil apoptosis. Neutrophil count and percentage of apoptotic neutrophils did not differ significantly between the groups. When frequency of infection episodes among groups was evaluated, frequency of infection episodes of the patients who were receiving DFO was significantly higher than in the other groups. When correlation between neutrophil apoptosis and frequency of infection episodes, serum ferritin levels, and neutrophil count of the patients was analyzed according to groups, no significant correlation was found. The results indicate that high serum ferritin level and DFO use in patients with g -thalassemia major do not enhance neutrophil apotosis in vivo and enhanced neutrophil apoptosis cannot be a possible cause for increased susceptibility to infections in these patients.

Role of transforming growth factor-beta 1 gene polymorphisms in childhood idiopathic thrombocytopenic purpura.

PURPOSE To investigate whether transforming growth factor-beta 1 (TGF-beta 1) gene polymorphisms have a role in the development, clinical progress, and treatment response in children with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS Thirty-five children with acute ITP, 40 children with chronic ITP, and 97 healthy children were enrolled. After genomic DNA was extracted, TGF-beta 1 gene 509 (C-->T), codon 25 (Arg-->Pro), and codon 10 (Leu-->Pro) polymorphisms were studied using a coupled polymerase chain reaction-restriction enzyme digestion method. RESULTS The genotype and allele frequencies of TGF-beta 1 polymorphisms between acute ITP, chronic ITP, and control group did not differ significantly. No significant association was found between TGF-beta 1 polymorphisms and therapy response. CONCLUSIONS These results demonstrate that the frequency of TGF-beta1 gene 509 (C-->T), codon 25 (Arg-->Pro), and codon 10 (Leu-->Pro) polymorphisms and alleles do not play a role as a genetic risk factor in the development and clinical progress of ITP. Different results may be obtained with further studies involving larger patient populations and other TGF-beta 1 gene polymorphisms.

Nutritional B12 Deficiency in Infants of Vitamin B12-Deficient Mothers

AIM Nutritional vitamin B₁₂ deficiency in infants may occur because the maternal diet contains inadequate animal products. Clinical presentations of the infants who had nutritional vitamin B₁₂ deficiency were analyzed in this study. SUBJECTS AND METHODS Patients with nutritional vitamin B₁₂ deficiency were enrolled in the study between 2003 and 2010. The diagnosis was based on a nutritional history of mothers and infants, clinical findings, hematological evaluation, and low level of serum vitamin B₁₂. RESULTS Thirty children aged 1 - 21 months constituted the study group. Poverty was the main cause of inadequate consumption of animal products of the mothers. All infants had predominantly breastfed. The most common symptoms were developmental delay, paleness, apathy, lethargy, anorexia, and failure to thrive. Hematological findings were megaloblastic anemia (83.3 %), thrombocytopenia (30 %), and severe anemia (13.3 %). All of the mothers had low serum B₁₂ levels; eight of them had megaloblastic anemia. CONCLUSION The unusual clinical manifestations of vitamin B₁₂ deficiency may also be seen apart from neurological and hematological findings. Nutritional vitamin B₁₂ deficiency due to maternal deficiency might be a serious health problem in infants. Therefore, screening and supplementation of pregnant and lactating women to prevent infantile vitamin B₁₂ deficiency should be considered.

Variant clinical courses in children with immune thrombocytopenic purpura: Sixteen year experience of a single medical center

OBJECTIVE Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia in children. The objective of this study was to evaluate the presenting features, variation in the clinical courses, initial response rate to therapy, and long-term outcome in patients with ITP. METHODS Three hundred and fifty out of 491 newly diagnosed patients with ITP between the initial diagnosis ages of 6 months to 16 years were included in this retrospective, descriptive study. Patients with acute vs chronic ITP, acute vs recurrent ITP and chronic vs recurrent ITP were compared in terms of age at diagnosis, gender, initial platelet count, response rate to initial therapy, long-term outcome, and total duration of follow-up. RESULTS The clinical courses of the patients were determined as acute, chronic and recurrent in 63.8%, 29.1%, and 7.1%, respectively. Platelet count >20x109/L and initial diagnosis age >10 years were found to increase the probability of chronic outcome by at least two-fold. CONCLUSION It is concluded that ITP in childhood is a common disease with low morbidity and mortality. In addition to the acute and chronic form, a rare recurrent form, which accounts for about 4-7% of all ITP patients, should be considered.