Growth retardation, general hypotonia, and loss of acquired neuromotor skills in the infants of mothers with cobalamin deficiency and the possible role of succinyl-CoA and glycine in the pathogenesis.

Vitamin B12 (cobalamin, Cbl) deficiency can cause metabolic, hematological, and neurological abnormalities. Adequate levels of succinyl-coenzyme A (CoA) cannot be synthesized from methylmalonyl-CoA because of the decreased activity of the methylmalonyl-CoA mutase enzyme that uses Cbl as the cofactor. Succinyl-CoA synthesis deficiency leads to decreased heme synthesis and gluconeogenesis. The reason of growth retardation can be gluconeogenesis deficiency together with heme synthesis deficiency whereas the reason of the neurological abnormalities can be glycine increase in the tissue due to decreased heme synthesis. We present 7 infants diagnosed with severe nutritional Cbl deficiency and discuss the role of succinyl-CoA and glycine in the possible pathogenesis in this article. Patients brought to our clinic with a complaint of growth retardation and diagnosed with nutritional Cbl deficiency were included in the study. There were 5 females and 2 males. The mean age was 11 ±â€Š2.30 (range 6-13) months. All patients had general muscular hypotonia and 4 had growth retardation. Neuromotor growth retardation was found in 4 of the children who had previously shown normal neuromotor development for age. The mean Cbl level was 83.8 ±â€Š27.6 (45.6-114) pg/mL. The mean Cbl level of the mothers was 155 ±â€Š56.6 (88-258) pg/mL. Six of the patients had anemia and 1 had thrombocytopenia. Mean corpuscular volume value was 91.5 ±â€Š12.2 fL. Following treatment, the muscle tonus of the patients improved, the anemia and growth retardation decreased, and the lost neuromotor abilities were recovered. Severe nutritional Cbl deficiency is an important nutritional disease where complications can be prevented with early treatment. When evaluating the pathogenesis, it should be noted that nutritional Cbl deficiency is a succinyl-CoA synthesis deficiency.

Citrate metabolism and its complications in non-massive blood transfusions: association with decompensated metabolic alkalosis+respiratory acidosis and serum electrolyte levels.

BACKGROUND AND OBJECTIVES: Metabolic alkalosis, which is a non-massive blood transfusion complication, is not reported in the literature although metabolic alkalosis dependent on citrate metabolism is reported to be a massive blood transfusion complication. The aim of this study was to investigate the effect of elevated carbon dioxide production due to citrate metabolism and serum electrolyte imbalance in patients who received frequent non-massive blood transfusions. MATERIALS AND METHODS: Fifteen inpatients who were diagnosed with different conditions and who received frequent blood transfusions (10-30 ml/kg/day) were prospectively evaluated. Patients who had initial metabolic alkalosis (bicarbonate>26 mmol/l), who needed at least one intensive blood transfusion in one-to-three days for a period of at least 15 days, and whose total transfusion amount did not fit the massive blood transfusion definition (<80 ml/kg) were included in the study. RESULTS: The estimated mean total citrate administered via blood and blood products was calculated as 43.2 ± 34.19 mg/kg/day (a total of 647.70 mg/kg in 15 days). Decompensated metabolic alkalosis+respiratory acidosis developed as a result of citrate metabolism. There was a positive correlation between cumulative amount of citrate and the use of fresh frozen plasma, venous blood pH, ionized calcium, serum-blood gas sodium and mortality, whereas there was a negative correlation between cumulative amount of citrate and serum calcium levels, serum phosphorus levels and amount of urine chloride. CONCLUSION: In non-massive, but frequent blood transfusions, elevated carbon dioxide production due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis+respiratory acidosis and electrolyte imbalance may develop. This situation may contribute to the increase in mortality. In conclusion, it should be noted that non-massive, but frequent blood transfusions may result in certain complications.

Biochemical, radiologic, ultrastructural, and genetic evaluation of iron overload in acute leukemia and iron-chelation therapy.

Iron overload in hereditary hemochromatosis and hematologic malignancy has unfavorable effects on morbidity. Herein, 53 children (age 108.4±58.3 mo, 25 girls and 28 boys) with acute myeloblastic and lymphoblastic leukemia, who received 4 different chemotherapy protocols, were evaluated for iron overload throughout chemotherapy. Iron overload arose: (1) before chemotherapy, which was dependent on neither chemotherapy nor packed red blood cell transfusions and (2) after chemotherapy, which was dependent on the duration and nature of chemotherapy and partially on transfusion of packed red blood cells. Iron overload was documented in 75% of patients with a ferritin level >1000 ng/mL, by liver and heart magnetic resonance imaging, and they were administered iron-chelation therapy with success. Three of 10 radiologically iron-overloaded patients were heterozygous for H63D mutation. Aminolevulinic acid and porphobilinogen levels were normal. Light microscopic examination of the bone marrow revealed increased iron granules in erythroblasts, platelets, and megakaryocytes, iron-laden macrophages, free iron in the matrix, dyshematopoiesis, and apoptotic cells. Electron microscopic examination revealed iron-laden secondary lysosomes and autolysosomes in normoblasts and iron-laden primary granules in promyelocytes, irrelevant to the ferritin level, implying autophagia due to chemotherapy as a source of the excess iron. We think that iron overload, which is an important complication of acute leukemia, should be evaluated separately from "transfusion overload," and the management principles specific to leukemia should be implemented.

Hemophagocytosis in a case with Crimean-Congo hemorrhagic fever and an overview of possible pathogenesis with current evidence.

Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic condition characterized by high fever, hepatosplenomegaly, cytopenia, hyperferritinemia, and increased hemophagocytic macrophage proliferation and activation in the reticuloendothelial system. Primary HLH is familial and is a fatal disease that begins during early childhood. Secondary HLH may be acquired after intense activation of the immune system due to infection. Clinical and biologic symptoms result from cytokines secreted by T-lymphocytes and macrophages. Subtypes of primary HLH are caused by genetic defects in several cell types, including perforin-dependent cytotoxic T-lymphocytes and natural killer (NK) cells. Secondary HLH is often associated with intracellular pathogen infections. Crimean-Congo hemorrhagic fever (CCHF) is caused by a tick-borne virus, Nairovirus, from the Bunyaviridae family. It is characterized by a poor prognosis and has a high mortality. We report the case of a 14-year-old boy living in a CCHF-endemic area with no history of tick exposure. He presented with fever, and laboratory tests showed bicytopenia and hemophagocytosis in the bone marrow aspiration. Blood samples were polymerase chain reaction (PCR)-negative for CCFH but immunoglobulin (Ig)M-positive. In conclusion, patients with hemophagocytosis should be assessed for CCHF during the evaluation of cytopenia.

False positive result of the direct antiglobulin test (DAT): the role of the elevated level of immunoglobulin G.

Direct antiglobulin test (DAT) is a test that shows antibodies bound to the surface antigens of erythrocytes. In this article, our aim was to investigate whether a correlation exists between a DAT positive test and serum immunoglobulin (Ig) levels. In our clinic, all DAT positive patients were retrospectively studied. Patients who had not received a blood transfusion within the last three months and who were evaluated for Ig levels were enrolled in the study (n = 15). Of these subjects, 15 showed a DAT positive result. Ten patients did not show any clinical or laboratory signs of hemolysis, while five patients exhibited signs and symptoms of autoimmune hemolytic anemia (AIHA). While all subjects showed a DAT positive test result (Ig G ± C(3)), four patients without AIHA, and three patients with AIHA showed a positive indirect antiglobulin test (IAT). In patients with a higher level of immunoglobulin G (IgG), the treatment of the concomitant disease resulted in normalization of the IgG level and led to a negative DAT test. The conditions that lead to an elevation of Ig should be reviewed in patients who displayed a DAT positive test without hemolysis and who had not previously received a blood transfusion.

H1N1-Associated Encephalitis in a Child with Acute Myeloblastic Leukemia and Bacteremia due to Klebsiella Pneumoniae.

Herein we present a neutropenic 16-year-old female with acute myeloblastic leukemia that developed recurrentgeneralized seizures while receiving antimicrobial therapy (including oseltamivir) due to pneumonia, bacteremiaof Klebsiella pneumoniae, and H1N1 infection. The patient's seizures were controlled using assisted ventilation.Electroencephalography showed that the patient had encephalopathy. Cranial computed tomography (CT), magneticresonance imaging (MRI), and MRI angiography findings were normal. The patient fully recovered without sequelae.This case indicates that during pandemics of influenza-like diseases H1N1 infection should always be a consideration.

Hematogones in immune thrombocytopenic purpura: diagnostic implication.

Hematogones (HGs) are benign immature B cells in bone marrow with a variety of benign and malignant conditions, including idiopathic thrombocytopenic purpura, leukemia, lymphoma, red blood cell aplasia, iron deficiency anemia, amegakaryocytosis, regenerative bone marrow following viral injury, chemotherapy or bone marrow transplantation, copper deficiency, autoimmune cytopenias, neuroblastoma, and acquired immunodeficiency syndrome (AIDS). HGs may cause diagnostic problems because of their morphologic and immunophenotypic similarities to neoplastic lymphoblasts. Herein, two patients with thrombocytopenia and three lineage dysplasias in the bone marrow suggesting myelodysplastic syndrome (MDS) with excess blasts are presented. Light microscopic evaluation of marrow from both patients revealed periodic acid-Schiff (PAS)-negative blasts However, flow cytometric analysis revealed excessive HGs in both patients, implying that the cells that were considered as blasts were actually large HGs. Thus, the patients were diagnosed as immune thrombocytopenic purpura due to the isolated thrombocytopenia, large platelets on blood and bone marrow smears and increased megakaryocytes in the bone marrow. These cases emphasize the importance of distinction of hematogone-rich conditions from leukemia and MDS for accurate diagnosis and treatment, and the reliability of multiparameter flow cytometry for the differential diagnosis.

Conus medullaris syndrome and acute colonic pseudoobstruction in a child with acute lymphoblastic leukemia.

A 5(3/12)-year-old boy with Philadelphia chromosome (+) pre-B acute lymphoblastic leukemia (ALL) without extramedullary involvement did not achieve remission after induction therapy. His family stopped therapy, but he was readmitted eight months later due to pyoderma, pneumonia and active leukemia with leukocytosis. During cytoreductive and antibiotic therapy, he developed progressive abdominal distension, pain, globe vesicale, tachypnea, and respiratory alkalosis. Bowel sounds could not be auscultated. Dilation, mainly in the large intestine, was detected radiologically. His neurological examination revealed absence of superficial reflexes and hypoesthesia along with normal motor strength and deep tendon reflexes in the lower extremities, consistent with conus medullaris syndrome, which was thought to give rise to acute colonic pseudo-obstruction.

Delayed diagnosis of acute leukemia in a patient with bone pain and fracture.

In childhood acute lymphoblastic leukemia (ALL), non-hematological manifestations involving the musculoskeletal system can also be encountered. These manifestations may cause a delay in the diagnosis of leukemia. The presented case in this report is a six-year-old boy who developed bone pain and long bone fracture and was diagnosed as ALL after a considerable delay. This case is presented to draw attention to the fact that leukemia must be considered in pediatric patients who present with bone manifestations.

A hemolysis trigger in glucose-6-phosphate dehydrogenase enzyme deficiency. Vicia sativa (Vetch).

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme, playing an important role in the redox metabolism of all aerobic cells. It was reported that certain medications, fava beans, and infections can trigger acute hemolytic anemia in patients with G6PD deficiency. An 8-year-old male patient was admitted to the hospital with blood in the urine, headache, dizziness, fatigue, loss of appetite, and jaundice in the eyes, 24 hours after eating large amounts of fresh, vetch grains. Laboratory investigation revealed hemolytic anemia, hyperbilirubinemia, and G6PD deficiency. Approximately 0.5% of fava bean seeds have 2 pyrimidine beta-glycosides called, vicine and convicine. Vetch has 0.731% vicine, 0.081% convicine, and 0.530% beta cyanoalanine glycosides. The aim of this case report is to emphasize the importance of vetch seeds as a cause for hemolytic crisis in our country, where approximately one million tons of vetch is produced per year, especially in the agricultural regions.

Outbreaks of tularemia in Turkey.

Tularemia, casued by Francisella tularensis, is a zoonotic disease presenting various clinical forms. In the present study, three outbreaks of tularemia occurred from January to March and September in 2004 (first and second) and January to March in 2005 (third) are reported from the north-eastern part of Turkey. All cases originated from the same geographical location. In total, 56 patients having complaints of fever, malaise, chills and shivering, painful sore throat with swollen tonsils and enlarged cervical lymph nodes were affected and the patients were different in all cases. Forty-four, 7 and 5 people were affected in the first, second and third outbreak, respectively. The sera from all patients were analysed for the presence of F. tularensis antibodies using a microagglutination assay. Overall, of the 56 sera analysed, 39 (33, 3 and 3 were from the first, second and third outbreak, respectively) showed antibody titres of 1/160 and/or more against F. tularensis. The current report suggests that tularemia exists in north-eastern part of Turkey. The clinical manifestation of the current cases were similar to those of oropharyngeal form of tularemia. It is considered that this region should be accepted as an endemic area for tularemia and kept under control for a long period.

The relationship of hypocalcemic convulsions related to nutritional rickets with age, gender, season, and serum phosphorus levels.

OBJECTIVE: To retrospectively evaluate the epidemic characteristics of children with hypocalcemic convulsion related to nutritional rickets in the province of Kars, Turkey. METHODS: In this study, clinical and laboratory findings of 93 infants, aged between 1-24 months, who were diagnosed as hypocalcemic convulsive resulting from nutritional rickets between January 2000 and June 2005 in Kars Maternity and Child Hospital, were investigated. The data of the cases with hypocalcemic convulsive rickets were collected from the hospital archive file. RESULTS: The mean and median ages of the cases were 8.93 and 6 (1-24) months, and 66 (71%) were male. Most of the patients were admitted to hospital in February and March, whereas 46% were admitted in winter, 44% in spring, 8% in autumn, and 2% in summertime. Serum calcium levels of all cases were low (mean: 5.4 +/- 0.84 mg/dl) and serum alkaline phosphate levels were high (mean: 1286 +/- 528 IU/L), while serum phosphorus levels were low in 19 (20.4%), high in 8 (8.6%), and normal in 66 (71%) patients. CONCLUSION: While evaluating the causes of convulsion, hypocalcemic convulsion related to nutritional rickets should be considered among the causes as well as age, gender, and season of the year, and diagnosis, and treatment should be initiated without delay. In addition, serum phosphorus level should also be questioned in the diagnosis of nutritional rickets.