Erythropoietin Concentration in Boys With p.His63Asp Polymorphism of the HFE Gene.

The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. HFE-related hemochromatosis is characterized by excessive intestinal absorption of dietary iron, in particular cases resulting in pathologically high iron storage in tissues and organs. During childhood, HFE gene homozygosity or heterozygosity manifests exclusively in the form of biochemical abnormalities. Because of their mutual link, bioavailable iron and endogenous erythropoietin (EPO) are indispensable for effective erythropoiesis. We analyzed the impact of p.(His63Asp) polymorphism of the HFE gene on erythropoiesis taking into consideration endogenous EPO production in the developmental age. In the study we performed, we observed a significant, strong and negative correlation between the concentration of EPO, hemoglobin, and red blood cell count. A negative trend was also noted on the impact of iron concentration and transferrin saturation on EPO production. In conclusion, this preliminary study demonstrates an impaired impact of endogenous EPO on erythropoiesis in the presence of increased iron content in carriers of p.(His63Asp) (heterozygotes) variant of the HFE gene in developmental age.

Marathon Run-induced Changes in the Erythropoietin-Erythroferrone-Hepcidin Axis are Iron Dependent.

Alterations in iron metabolism after physical activity are manifested through the rise of blood hepcidin (Hpc) levels. However, in many athletes, no changes in Hpc levels are observed after exercise despite the presence of inflammation. The missing links could be erythropoietin (EPO) and erythroferrone (ERFE), which down-regulate Hpc biosynthesis. EPO, ERFE and Hpc biosynthesis is modified by serum iron through transferrin receptor 2. Consequently, we investigated whether marathon-induced changes in EPO, ERFE and Hpc levels are blood iron-dependent. Twenty-nine healthy male marathon runners were analyzed. Serum iron, ferritin, transferrin, EPO, ERFE and Hpc levels were assessed before, immediately after, and 9 ± 2 days after the marathon. The runners whose serum Hpc decreased after the marathon (n = 15), showed a significant increase in ERFE levels. In athletes whose serum iron levels were below 105 µg/day (n = 15), serum EPO (p = 0.00) and ERFE levels (p = 0.00) increased with no changes in Hpc concentration. However, in athletes with low serum iron, no changes in EPO levels were observed when serum ferritin exceeded 70 ng/mL (n = 7). Conversely, an increase in ERFE levels was observed in marathoners with low serum iron, independently of serum ferritin (n = 7). This indicates modulation of blood iron may affect exercise-induced changes in the EPO/ERFE/Hpc axis. Further study is needed to fully understand the physiological meaning of the interdependence between iron and the EPO/ERFE/Hpc axis.

Impairment of lung diffusion capacity-a new consequence in the long-term childhood leukaemia survivors.

Childhood leukaemia survivors (CLS) are known to have developed long-term impairment of lung function. The reasons for that complication are only partially known. The aims of this study were to assess pulmonary function in CLS and identify (1) risk factors and (2) clinical manifestations for the impairment of airflow and lung diffusion. The study group included 74 CLS: 46 treated with chemotherapy alone (HSCT-), 28 with chemotherapy and haematopoietic stem cell transplantation (HSCT+), and 84 healthy subjects (control group (CG)). Spirometry and diffusion limit of carbon monoxide (DLCO) tests were performed in all subjects. Ten (14%) survivors had restrictive, five (7%) had obstructive pattern, and 47 (66%) had reduced DLCO. The age at diagnosis, type of transplant, and type of conditioning regimen did not significantly affect the pulmonary function tests. The DLCO%pv were lower in CLS than in CG (p < 0.03) and in the HSCT+ than in the HSCT- survivors (p < 0.05). The pulmonary infection increased the risk of diffusion impairment (OR 5.1, CI 1.16-22.9, p = 0.019). DLCO was reduced in survivors who experienced CMV lung infection (p < 0.001). The main symptom of impaired lung diffusion was poor tolerance of exercise (p < 0.005). The lower lung diffusion capacity is the most frequent abnormality in CLS. HSCT and pulmonary infection, in particular with CMV infection, are strong risk factors for impairment of lung diffusion capacity in CLS. Clinical manifestation of DLCO impairment is poor exercise tolerance. A screening for respiratory abnormalities in CLS seems to be of significant importance.

[Hfeprotein impact on iron metabolism].

Hereditary hemochromatosis type 1 is an autosomal recessive disorder caused by HFE gene mutations, which is an iron homeostasis metabolism controlling co-factor. Adults with male predomination present with clinical symptoms derived by iron overload in organs. The phenotype expression is individual with an influence of individual and environmental factors. Despite the fact that HFE variants are widespread, its impact still remains unknown. The article reviews the literature considering the role of HFE gene mutations regarding its impact in children.

HFE Gene Mutations and Iron Status in 100 Healthy Polish Children.

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.

Reduction of Skeletal Muscle Power in Adolescent Males Carrying H63D Mutation in the HFE Gene.

Iron overload resulting from the mutation of genes involved in iron metabolism or excess dietary intake has been reported to negatively influence human physical performance. The aim of this study was to test the hypothesis that adolescents bearing a hemochromatosis gene (HFE) mutation in contrast to adults with the same mutation will not experience iron accumulation and their aerobic capacity will be similar to that of age-matched controls. Thirteen boys participated in the study. Seven of them are carriers of H63D mutation in the HFE gene and six were wild type. Fitness levels were assessed using the cardiopulmonary exercise test. In addition, iron status and inflammatory markers were determined. We observed that cardiovascular fitness was significantly lower in the group bearing the HFE mutation compared to the control group. Moreover, the HFE mutation group achieved lower maximal power output compared to the control group. There were no differences in blood ferritin concentrations between the two groups which indicates similar amounts of stored iron. Obtained data do not confirm our hypothesis. On the contrary, it was demonstrated that HFE mutation is associated with a lower level of aerobic capacity, even in the absence of iron accumulation.

[Hereditary hemochromatosis in children].

Iron is a micronutrient which is essential for the existence of organisms. This element participates in oxygen transport, as well as energetic, metabolic and immunologiocal processes. Disturbances of iron homeostasis lead to multiorgan dysfunction. Iron deficiency anemia is a common disorder in childhood, while iron overload is rarely observed in the developmental age. There are primary and secondary reasons for iron overload. Hereditary hemochromatosis is a metabolic disorder caused by the mutations of genes that control iron metabolism leading to increased intestinal absorption. Secondary hemochromatosis is caused by multiple transfusions, chronic hemolysis, or iron pills and iron-rich food intake. The article reviews the literature devoted to primary iron overload in childhood.

[Prolonged leucopenia in asymptomatic children]. / Przedluzajaca sie leukopenia u dzieci bez objawów chorobowych.

INTRODUCTION: The term leucopenia is still a challenge for clinicists in cases of unknown reasons. There are two main groups of leucopenia: 1. Severe, chronic leucopenia (cyclic, inborn, and idiopathic); 2. Acquired or secondary (reasons: some drugs, infections, viral mainly, autoimmune diseases, haematological abnormalities, neoplasms, hiperspleenism and metabolic diseases). The aim of this investigation was an analysis of asymptomatic, lasting over three months leucopenia myelograms of childhood. MATERIAL AND METHODS: 21 children (6 girls and 15 boys, aged 10-17 years, mean 13.6, median 12 years) were analysed. The children were referred to our clinic by family physicians to investigate the reason of asymptomatic, lasting over three months leucopenia. These children are still under our observation from one till four years. Despite the fact of lasting over three months leucopenia, the general condition of the patients is good. In all the patients the myelogram analysis was performed after May-Grumwald-Giemsa dying, three slides of one hundred cells were counted. Statistical analysis was made using STATISTICA (Stat Soft Polska) programme. RESULTS: Mean number of leucocytes was 3.06x109/ l (median 2.75x109/l, values from 2.46x109/l to 3.53x109/l), mean number of neutrocytes was 1.15x109/l (median 1.07 x 109/l, values from 0.62x109/l to 1470x109/l). Hemoglobin concentration and platelets number were normal. Mean number of marrow cells were within references. However mean number of myelocytes, metamyelocytes, bands and eosynophils were lower than mean number of general population marrow cells (p<0.05). Mean values of myeloblasts, neutrophils, and monocytes were statistically higher than in general population (p<0.05). CONCLUSIONS: 1. Hypothesis of obtained differencess in numer of marrow cells would need to be investigated in broad population of patients. 2. Considering that three children presented with positive familial leucopenia history (in one of them grandmother, in two anothers fathers) genetic predisposition can be expected.

Anemia secondary to valproic acid therapy in a 13-year-old boy: a case report.

INTRODUCTION: Valproic acid is a commonly used anti-epileptic drug. Hematological toxicities are among the occasionally observed adverse effects of this medication. CASE PRESENTATION: We present the case of a 13-year-old Caucasian boy who demonstrated mild anemia 12 months after the introduction of valproic acid therapy. A bone marrow biopsy revealed maturation arrest of proerythroblasts. CONCLUSION: Prompt diagnosis and valproic acid discontinuation resulted in the patient's recovery.

Methemoglobinemia in postchemotherapy stomatitis topical treatment: 2 pediatric cases.

Methemoglobinemia is a rare congenital or acquired disease of increased blood methemoglobin concentration. We documented 2 cases of children suffering from neuroblastoma whose postchemotherapy anemia, leucopenia, and stomatitis were complicated by methemoglobinemia after using a formulary oral gel (7.5% benzocaine, doxycycline, nystatin, glycerin). The complication resulted in hospital treatment. Percutaneous oxygen saturation remained at 85% and 87% despite administration of 100% oxygen through a nonrebreather mask. Arterial blood gas analysis showed an oxygen saturation of 98% and 97%, respectively. Spectroscopic measurement showed methemoglobin concentration of 42% and 35.5%, respectively. After red blood cell transfusion and oral ascorbic acid in case 1 and methylene blue in case 2, the patients' condition improved. Although the benzocaine gel is not in use in several medical systems, it should be considered as a possible reason for methemoglobinemia.

[Budd-Chiari syndrome in 16 year old girl with essential thrombocytosis]. / Zespol Budda-Chiariego u 16-letniej dziewczynki z nadplytkowoscia samoistna.

Vein thrombosis is a rare disorder diagnosed in childhood. The principal causes of this illness are inborn thrombophilias, essential thrombocytosis, neoplasms, autoimmunologic diseases and pathologic reaction to certain drugs. Budd-Chiari syndrome, a hepatic vein occlusion is an atypical manifestation of vein thrombosis. Due to the abundant symptomatology, interdisciplinary diagnostic procedures and serious prognosis the Budd-Chiari syndrome is a challenge for contemporary medicine. We present a 16 years old girl with essential thrombocytosis, the complicated by hepatic vein thrombosis.

Does antineoplasm treatment decrease the glomerular filtration rate in children?

BACKGROUND: The aim of this cross-sectional study was to test the hypothesis that children diagnosed with nephroblastoma experience increased disturbance in renal filtration even after prompt treatment compared to patients treated for other neoplastic childhood diseases. PROCEDURES: Our study included 127 children and young adults, who were successfully treated for nephroblastoma (n = 34), oncohaematological childhood diseases (n = 58), and other solid tumours (n = 35). In each patient, serum levels of cystatin C, microalbuminuria, and C-reactive protein, and serum and urine levels of creatinine were examined, along with a urine analysis. The estimated glomerular filtration rate (eGFR) was assessed using the Schwartz formula and Filler's formula. RESULTS: Our studies show that patients who were successfully treated for nephroblastoma and other solid tumours have lower GFR (GFR(Sch) 118 +/- 20, p = 0.00006, and 117 +/- 22, p = 0.00003; GFR(Filler) 99 +/- 17, p = 0.0001, and 104 +/- 21 ml/min/1.73 m(2), p = 0.0002) than children treated for oncohaematological diseases (GFR(Sch) 137 +/- 19, GFR(Filler) 121 +/- 18 ml/min/1.73 m(2)). CONCLUSIONS: Patients diagnosed with nephroblastoma and other solid tumours have lower eGFR than children with oncohaematological childhood diseases and are at higher risk for developing CKD. This study demonstrates the necessity of nephrological monitoring.

[Neutropenia in infancy - sometimes chronic and benign - own experiences]. / Neutropenia niemowleca - czasem przewlekla i lagodna - obserwacje wlasne.

Chronic neutropenia is a decrease in circulating neutrophils in the peripheral blood lasting over 6 months. Values need to be refered with the age and race. In children aged 2 weeks to 12 months reffered values are above 1000/03BCL. There are congenital and aquired reasons of neutropenia in infancy. The most common type of chronic neutropenia in infants is chronic, benign neutropenia (AIN). Authors present ten infants between three and six months with chronic, benign neutropenia. The reason of ordering laboratory tests at outpatient clinic were benign upper respiratory tract infections (four cases), pallor (four cases) and on parental demand (one case). In one infant neutropenia was observed during treatment of pneumonia at a district hospital.

[Second neoplasms in children with solid tumours in the years 1992-2007. Experiences of Gdansk medical academy]. / Drugie nowoteory u dzieci z guzami litymi w latach 1992-2007. Doswiadczenia osrodka gdanskiego

UNLABELLED: The occurrence of a second tumour is a severe complication of neoplastic disease and its treatment, and it reduces the patient's chances to survive. The aim of the study was to assess the frequency of a second neoplasm and its clinical course in children treated in Gdansk in the years 1992-2007. PATIENTS AND METHODS: There were 420 children and young adults included in the study. They were treated for malignant tumours in this period in the Department of Paediatrics, Haematology, Oncology and Endocrinology Medical Academy of Gdansk. The medical records of these patients were analysed. RESULTS: The second neoplasm was diagnosed in 9 patients, aged 9 to 23 years. They were treated for nephroblastoma - 3 cases, soft tissue sarcoma - 2, Ewing's sarcoma - 1, medulloblastoma - 1, retinoblastoma - 1 and neuroblastoma - 1 case. The second neoplasms were: acute non lymphoblastic leukaemia - 2, soft tissue sarcoma - 2, osteosarcoma - 2, chondrosarcoma - 1, renal cell carcinoma - 1 and glioblastoma multiforme - 1 case. Time between the first and second diagnosis was from 3 and 11/12 to 19 years. Treatment failed in 5 out of 9 children treated for osteosarcoma (2/2), chondrosarcoma (1/1), soft tissue sarcoma (1/2) and acute non lymphoblastic leukaemia (1/2). These patients died of progression of neoplastic disease during 2 to 20 months after the diagnosis of the second tumour. CONCLUSIONS: The diagnosis of the second tumour worsens the prognosis. It is difficult to define the factors that predispose to the second neoplasm. In 5 cases the second neoplasm occurred in the region which was previously irradiated.

[Thalassemia beta in children from Pomerania Region]. / Thalassemia beta u dzieci z Województwa Pomorskiego.

The thalassemias are inherited disorders resulting from deficient synthesis of one or more polypeptide chains of normal haemoglobin. There are two main groups of thalassemia: alpha and more common beta. The carriage of thalassemia genes are widely spread and the disease is considered the most common genetic disorder worldwide. Thalassemias are particularly prevalent in inhabitants of Italy, Greece, Spain, Mediterranean Islands, West Africa and some parts of Asia. The most common thalassemia beta cases are characterized from asymptomatic to severe microcytic anaemia with hepatosplenomegaly and physical development disturbances. The authors present eight unrelated children from the Pomerania Region of Poland complaining of chronic microcytic anaemia with normal iron level. Elevated level of haemoglobin A2 and in some of them haemoglobin F revealed thalassemia beta.

Compound heterozygote (C282Y/H63D) of hereditary hemochromatosis in a 16-year-old girl with hypoplastic kidney.

Iron-overload diseases are associated with primary or secondary disturbances of iron metabolism. Hereditary hemochromatosis, a genetically heterogeneous disease that is characterized by increased iron absorption and progressive deposition in parenchymal cells, may lead to organ damage and failure. Molecular studies have shown that hemochromatosis type 1 is predominantly due to a mutation in the HFE gene; there are 2 major mutations (C282Y and H63D). Disease symptoms are observed mostly after 40 years of age, often in men. We report the unusual case of a 16-year-old girl with an elevated serum iron level and a hypoplastic kidney. Identification of heterozygosity for the HFE gene mutation C282Y/H63D confirmed the diagnosis of hemochromatosis type 1. The early detection of hemochromatosis in the presented case may delay organ damage and failure due to iron overload.