Screening of Variations in CD22 Gene in Children with B-Precursor Acute Lymphoblastic Leukemia.

BACKGROUND: CD22 is expressed on the surface of B-cell lineage cells from the early progenitor stage of pro-B cell until terminal differentiation to mature B cells. It plays a role in signal transduction and as a regulator of B-cell receptor signaling in B-cell development. OBJECTIVES: We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants that could play role in the pathogenesis of pre-B ALL in Turkish children. METHODS: This study included 109 Turkish children with pre-B ALL who were diagnosed at Losante Hospital for Children with Leukemia. Genomic DNA was extracted from both peripheral blood and bone marrow leukocytes. Gene amplification was performed with PCR, and all samples were screened for the variants by single strand conformation polymorphism. Samples showing band shifts were sequenced on an automated sequencer. RESULTS: In our patient group a total of 9 variants were identified in the CD22 gene by sequencing: a novel variant in intron 10 (T2199G); a missense variant in exon 12; 5 intronic variants between exon 12 and intron 13; a novel intronic variant (C2424T); and a synonymous in exon 13. Thirteen of 109 children (11.9%) carried the T2199G novel intronic variant located in intron 10, and 17 of 109 children (15.6%) carried the C2424T novel intronic variant. CONCLUSION: Novel variants in the CD22 gene in children with pre-B ALL in Turkey that are not present, in the Human Gene Mutation Database or NCBI SNP database, were found.

Evaluation of lipid peroxidation and antioxidant system in healthy iron-replete infants receiving iron prophylaxis.

OBJECTIVE: Iron supplementation is commonly recommended for infants; however, there are some reports that it causes oxidative damage. The aim of this study was to investigate the potential effects of iron supplementation at 4 mo of age, for a period of 2 mo, on lipid peroxidation and free radical scavenging enzymes. METHODS: Twenty-seven healthy 4-mo-old infants chosen randomly and given iron supplementation (ferrous sulfate, 10 mg of elemental iron per day) constituted the study group and 26 healthy 4-mo-old infants who were chosen randomly and not given iron supplementation constituted the control group. Weight, height, head circumference, complete blood cell count, serum ferritin level and intraerythrocytic zinc, iron, copper, malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase levels were measured in the two groups at 4 and 6 mo of life. RESULTS: Compared with controls at 6 mo of age, no significant differences were observed for intraerythrocytic zinc (0.5 ± 0.1 versus 0.6 ± 0.2 µg/mL, P > 0.05), copper (0.2 ± 0.1 versus 0.2 ± 0.2 µg/mL, P > 0.05), iron (130.8 ± 10.9 versus 127.4 ± 11.1 µg/mL, P > 0.05), malondialdehyde (21.4 ± 3.5 versus 22.4 ± 2.3 nmol/g of hemoglobin, P > 0.05), catalase (135.4 ± 23.9 versus 135.1 ± 23.3 MU/g of hemoglobin, P > 0.05), superoxide dismutase (1736.4 ± 141.1 versus 1701.3 ± 103.9 U/g of hemoglobin, P > 0.05), and glutathione peroxidase (8.9 ± 1.6 versus 8.4 ± 1.6 U/g of hemoglobin, P > 0.05) levels. CONCLUSION: Our study indicates that the supplemental use of elemental iron 10 mg/d for a period of 2 mo in healthy iron-replete infants did not cause lipid peroxidation or an impairment of antioxidant status.

Platelet aggregation in children with Helicobacter pylori infection.

This study was performed to investigate the platelet aggregation alterations in platelet-rich plasma (PRP) samples of children with Helicobacter pylori (H pylori) infection. Platelet aggregation induced by adenosine diphosphate (ADP), collagen, ristocetin, or epinephrine was studied with photometric aggregometry in 30 patients before and after eradication therapy and in a control group including 15 children. The pretreatment mean maximum aggregation values and slope were significantly lower (P < .0001) in the study group at 10 µmol/L concentrations of ADP (ADP-like defect). The maximum aggregation values and slope revealed no significant differences (P > 0.05) between the study group after therapy and the control group. We concluded that H pylori infection may cause dysfunction of platelets in children and can be reversed by H pylori eradication therapy. Further studies should be carried out to determine the mechanisms of platelet dysfunction in children with H pylori infection.

High dose calcitriol in osteopetrorickets.

Osteopetrorickets is a rare autosomal recessive disorder of osteoclast function characterized by abnormally dense bone and failure of resorption of calcified cartilage. Rickets is a paradoxical complication of osteopetrosis, resulting from the inability of the osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. We report a patient with an unusual case of infantile osteopetro-rickets who was admitted with anterior fontanel bulging and was treated with haploidentical bone marrow transplantation.

Neutrophil hypersegmentation in children receiving angiotensin converting enzyme inhibitors.

Captopril and enalapril are the most commonly used angiotensin converting enzyme inhibitors in several cardiac diseases in children. On the other hand, the intrinsic renin-angiotensin system in the bone marrow might affect the growth of hematopoietic colonies and cellular production, proliferation and differentiation in physiological and pathological states. Starting with the hypothesis that inhibition of the renin-angiotensin system may have some effects on the hematopoietic system, including morphological changes within the granulocytes, we thus aimed to investigate prospectively whether the use of angiotensin converting enzyme inhibitors has any effect on the morphology, and especially segmentation, of neutrophils in peripheral blood. A total of 40 children with various heart diseases receiving either of two angiotensin converting enzyme inhibitors (captopril or enalapril) aged between 2 to 16 years were enrolled, and 40 healthy age- and sex-matched children were enrolled as controls. Complete blood count, peripheral blood smear, liver and renal function tests, and measurement of serum alkaline phosphatase, ferritin, vitamin B12 and folate levels were performed in all cases. Peripheral blood smears were viewed by two pediatric hematologists in a blinded manner. Neutrophil hypersegmentation was described as presence of five or more neutrophils with five well-separated lobes or at least one neutrophil with six or more lobes among 100 segmented neutrophils. The number of patients with neutrophil hypersegmentation in the study group was significantly higher than in the control group, and the mean lobe count in the study group was significantly higher than in the control group. Neutrophil hypersegmentation, as detected in patients using angiotensin converting enzyme inhibitors in the present study, has not been reported previously. Further studies aiming to explain the pathophysiological mechanism(s) underlying neutrophil hypersegmentation in patients receiving angiotensin converting enzyme inhibitors are needed.

Nosocomial outbreak of Sphingomonas paucimobilis bacteremia in a hemato/oncology unit.

Nosocomial Sphingomonas paucimobilis infections can arise from contaminated water and the contaminated hands of hospital staff. Within a 1-month period, we isolated six S. paucimobilis strains, including four from blood cultures of four patients and two from hospital environment specimens including tap water and a bathtub in a hemato/oncology unit. We described here these strains' molecular epidemiological analyses by pulsed-field gel electrophoresis (PFGE) and antibiotic susceptibilities by E-test. Although clinical and environmental isolates yielded three different antibiotic resistances and PFGE patterns, all four clinical strains had an identical pattern by both methods. Thus, the isolated clinical strain clone could be traced neither to health care workers nor to environmental samples. It was concluded that S. paucimobilis strains can cause outbreaks in hemato/oncology units. We did not demonstrate genetic relatedness between clinical and environmental isolates by PFGE, but did find PFGE a useful identification technique for epidemiological investigation.

Immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia and mumps.

Immune thrombocytopenic purpura in childhood is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child. In children it usually follows a viral infection (eg, mumps, rubella) or immunization. We report for the first time a child with acute lymphoblastic leukemia who developed immune thrombocytopenic purpura due to mumps during the maintenance phase of acute lymphoblastic leukemia treatment.

Effects of iron deficiency versus iron deficiency anemia on brainstem auditory evoked potentials in infancy.

There has been little or no evidence of brainstem auditory evoked potentials (BAEPs) among infants with iron deficiency (ID) that is not severe enough to cause anemia. To our knowledge, the effect of ID on auditory functions and/or potentials has not been investigated previously, though it seems reasonable that it should be associated with BAEP measures intermediate between those observed in iron deficiency anemia (IDA) and in iron sufficiency, considering the role of iron in myelin formation and maintenance. We therefore aimed in this study to investigate the effect of ID on BAEPs by comparing three groups of infants with ID, IDA and iron sufficiency (control) both before and after iron treatment (in iron-deficient groups). Three groups of infants (IDA, n = 25; ID, n = 24; Control, n = 44) were compared on the basis of hematological laboratory parameters and BAEP measurements both at entry into and after (12 weeks treatment with oral iron in IDA and ID groups) the study. BAEP measurements recorded at 85 dB both at entry into and after the study were not significantly different among the groups, although a sufficient response to iron treatment was achieved in iron-deficient groups (Group I and Group II). The only positive finding determined in our study was a slight decrease in latencies obtained at the end of the study when compared to the pre-study values in all three groups of the study in accordance with the expected age-dependent developmental changes. Although no negative electrophysiological effect of ID on brainstem auditory functions was found in the present study, further longer term (late childhood or adult) studies are necessary to elucidate the relationships among anemia (maybe other than IDA), ID and auditory functions, and clinical implications of hearing loss (if any) should be questioned.

Renal tubular function in children with beta-thalassemia minor.

BACKGROUND: beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. METHODS: The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. RESULTS: There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). CONCLUSION: On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

Familial high factor VIII level in a child with necrotizing fasciitis complicating primary varicella infection.

This article describes an unusual association of familial high plasma factor VIII level and necrotizing fasciitis in a 4-year-old girl with primary varicella infection.

Recombinant activated factor VII for severe gastrointestinal bleeding after chemotherapy in an infant with acute megakaryoblastic leukemia.

Recombinant activated factor VII (rFVIIa) is a major alternative for management of hemophiliac patients with inhibitors. Additionally, it has been used off-label for the treatment of massive life-threatening hemorrhage associated with various bleeding situations. Herein, we describe a 16-month-old boy with acute megakaryoblastic leukemia and severe intractable gastrointestinal bleeding controlled by rFVIIa. rFVIIa should be considered as a novel treatment alternative in severe bleeding conditions including leukemias that may have hemostatic defects and platelet dysfunction.

Mycoplasma pneumoniae infection in a child after renal transplantation.

Although Mycoplasma pneumoniae infections are common among school children and young adults, they have been rarely reported in renal transplant recipients. Herein, we report an 8-yr-old boy who had M. pneumoniae infection 1 yr after transplantation and showed liver dysfunction during the course of the disease. In children who underwent renal transplantation and receive immunosuppressive treatment, we suggest that symptoms of a simple upper respiratory tract infection may precede M. pneumoniae disease with potentially serious extrapulmonary complications.

Complete platelet recovery after treatment of Helicobacter pylori infection in a child with chronic immune thrombocytopenic purpura: a case report.

Helicobacter pylori gastritis has been associated with autoimmune disease, including immune thrombocytopenic purpura (ITP). The most recent reports also have supported this association in adults. ITP in children differs from that in adults in terms of clinical picture and mechanisms of thrombocytopenia. The authors report a case of a 12-year-old boy with chronic ITP, in whom they detected H. pylori infection and observed a complete platelet recovery after the eradication of H. pylori.

Factor VIII levels in children with thrombosis.

BACKGROUND: A number of coagulation defects have been implicated as risk factors in thrombo-embolic disease. Of these, high levels of clotting factor VIII have been shown to be associated with a five- to six-fold increased risk of thrombosis, compared to levels < 100 IU/dL in adults. The objective of this study was to investigate the prevalence of elevated plasma levels of factor VIII in a pediatric population with thrombo-embolism (TE). METHODS: Forty-two children (17 female, 25 male) with TE and 165 healthy controls without familial history of thrombosis or stroke were included in the present study. Doppler ultrasonography with or without angiography, computed tomography, magnetic resonance imaging or echocardiography was utilized to establish the diagnosis. One-stage clotting assay with factor VIII-deficient plasma for measurement of factor VIII and immunoturbidometric assay for von Willebrand factor (vWF) levels were utilized. All measurements were performed in duplicate. Plasma levels of factor VIII were assessed in parents of nine patients to establish whether high levels of factor VIII were genetically determined. RESULTS: The median age at onset of TE was 7 years (range 0-17 years). Among patients with TE compared to controls, the prevalence of high factor VIII levels was 59.5% versus 12.1% (odds ratio 10.6, 95% CI: 4.9-23.1). The prevalence of high factor VIII levels was detected in at least one of nine families. CONCLUSION: The data in the present study provide evidence that elevated plasma factor VIII levels are associated with increased risk of thrombosis in children: thus, plasma concentration of factor VIII should be measured in all children with TE.

Recurrent arterial thrombosis in a child: primary antiphospholipid antibody syndrome.

Antiphospholipid antibody syndrome (APS) is characterized by the association of recurrent arterial or venous thrombosis or recurrent fetal wastage and the presence of circulating antiphospholipid antibodies, detected as anticardiolipin antibodies or lupus anticoagulant. The authors report an 8-year-old girl, who presented with central retinal artery occlusion and live do reticularis and was diagnosed as APS. Despite the proper anticoagulant treatment she had several cerebral ischemic events and died 29 months after the diagnosis. A larger number of pediatric case investigations will be required for better understanding and treating this rare thrombotic disorder.