A Novel Tandem Mass Spectrometry Method for Rapid Confirmation of Medium- and Very Long-Chain acyl-CoA Dehydrogenase Deficiency in Newborns

BACKGROUND:Newborn screening for medium- and very long-chain acyl-CoA dehydrogenase (MCAD and VLCAD, respectively) deficiency, using acylcarnitine profiling with tandem mass spectrometry, has increased the number of patients with fatty acid oxidation disorders due to the identification of additional milder, and so far silent, phenotypes. However, especially for VLCADD, the acylcarnitine profile can not constitute the sole parameter in order to reliably confirm disease. Therefore, we developed a new liquid chromatography tandem mass spectrometry (LC-MS/MS) method to rapidly determine both MCAD- and/or VLCAD-activity in human lymphocytes in order to confirm diagnosis. METHODOLOGY:LC-MS/MS was used to measure MCAD- or VLCAD-catalyzed production of enoyl-CoA and hydroxyacyl-CoA, in human lymphocytes. PRINCIPAL FINDINGS:VLCAD activity in controls was 6.95+/-0.42 mU/mg (range 1.95 to 11.91 mU/mg). Residual VLCAD activity of 4 patients with confirmed VLCAD-deficiency was between 0.3 and 1.1%. Heterozygous ACADVL mutation carriers showed residual VLCAD activities of 23.7 to 54.2%. MCAD activity in controls was 2.38+/-0.18 mU/mg. In total, 28 patients with suspected MCAD-deficiency were assayed. Nearly all patients with residual MCAD activities below 2.5% were homozygous 985A>G carriers. MCAD-deficient patients with one other than the 985A>G mutation had higher MCAD residual activities, ranging from 5.7 to 13.9%. All patients with the 199T>C mutation had residual activities above 10%. CONCLUSIONS:Our newly developed LC-MS/MS method is able to provide ample sensitivity to correctly and rapidly determine MCAD and VLCAD residual activity in human lymphocytes. Importantly, based on measured MCAD residual activities in correlation with genotype, new insights were obtained on the expected clinical phenotype

Assesment of children with allergic rhinitis living in Kirikkale region

Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology - JUN 11-15, 2016 - Vienna, AUSTRIAWOS: 000383679802238European Acad Allergy & Clin Immuno

Assesment of children with allergic rhinitis living in Kirikkale region

Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology -- JUN 11-15, 2016 -- Vienna, AUSTRIAWOS: 000383679802238…European Acad Allergy & Clin Immuno

Cerebral MRI findings in neonatal hypoglycemia

Metabolic disturbances such as anoxia and hypoglycemia may adversely alter the development of the neonatal brain. While rapid and appropriate diagnosis with adequate therapy has a good prognosis; delayed detection and/or inappropriate therapy increases the risk of the development of irreversible brain damage. Magnetic resonance imaging (MRI) studies are essential in neonatal hypoglycemia to define the characteristics and severity of cerebral lesions after hypoglycemia, to decide the efficacy of preferred treatment modality and to predict the neurologic outcome. Although acute and long-term radiologic abnormalities associated with hypoglycemic episodes in children and adults are well documented, the details of the situation for neonatal hypoglycemia are still emerging. In this review, the impact of MRI findings of neonatal hypoglycemia on diagnosis, monitoring of treatment and neurologic outcome was discussed. © 2005 - IOS Press and the authors. All rights reserved

Long-term MRI findings of a case with persistent hyperinsulinemic hypoglycemia of infancy (nesidioblastosis)

Background and purpose: To describe the sequential magnetic resonance imaging (MRI) findings in a neurologically handicapped newborn who had been suffered from neonatal hypoglycemia due to persistent hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) and to evaluate the following changes in the long-term radiological follow-up. Case: A case of newborn with severe hypoglycemia due to nesidioblastosis is reported. The patient was presented with poor feeding, irritability, and seizures. Nesidioblastosis was diagnosed on the basis of high intravenous glucose requirement, high insulin to glucose ratio, negative urinary ketones. Normoglycemia was maintained by a combined treatment including glucose infusions and steroid, and then somatostatin analoques. The patient was assessed neurologically and radiologically by sequential cerebral MRI within 2 years follow-up. Results: The most striking findings were cystic lesions on corona radiata, parietooccipital deep white matter and diffuse subcortical involvement of the brain at the initial MRI. The lesions were recovered radiologically at the 5 months of age. Diffuse hyperintensity of the periventricular white matter and optic radiation suggests abnormal and delayed myelination at 1 year of age, and periventricular leukomalacia and ventricular irregularity at 2 years of age. More delayed neurologic sequelae included mental retardation and spasticity. Conclusion: Neonatal hyperinsulinemic hypoglycemia must be suddenly and appropriately diagnosed and treated to prevent any further neurological dysfunction and damage. MRI studies are crucial in nesidioblastosis to define the characteristics and severity of cerebral lesions after hypoglycemia. Long-term radiologic follow-up should be further investigated to predict the neurologic outcome, although the radiologic recovery period was seen in acute or subacute phase of the disease. © 2006 Elsevier Ireland Ltd. All rights reserved

Neonatal and maternal serum levels of soluble ICAM-1 in preeclamptic and normal pregnancies

The aim of this study is to determine whether circulating levels of sICAM-1 were changed in infants of preeclamptic mothers, and factors influencing these levels. Peripheral venous blood samples were obtained from preeclamptic and nonpreeclamptic pregnant women (control) and their babies in the first 2 hours post partum. The enzyme-linked immunoadsorbent assay (ELISA) technique was used to determine concentrations of sICAM-1. Compared with the control group, maternal and neonatal serum sICAM-1 levels were higher in the preeclamptic group. Neonatal levels were correlated with the maternal levels only, and there were no difference between premature and term babies and their mothers. In the control group, on the other hand, premature babies and their mothers had higher sICAM-1 levels than term babies and their mothers, with values close to those of premature group in the preeclamptic group. Neonatal sICAM-1 levels were correlated with gestational age, birth weight, and also with maternal levels. Linear regression analysis of these parameters, however, showed that only the gestational age was significant. The study suggests that perinatal sICAM-1 levels possibly are not independent from the maternal levels. High sICAM-1 levels in infants of preeclamptic mothers and premature babies might reflect the high maternal levels

Carnitinuria in rickets due to vitamin D deficiency

In this study, we measured the serum-urine total carnitine levels and PTH levels before and after treatment in 18 patients with nutritional rickets. The urine and blood samples were taken on the first (pretreatment) and the 15(th) day of the study (post-treatment). The total carnitine levels of serum and urine somples, serum PTH and serum-urine creatinine concentrations were determined. We found that the levels of carnitine excreted in the mine on the first (pre-treatment) and on the 15(th) day (post-treatment) were higher than the reference levels. Decrease in carnitine excretion on the 15(th) day seemed to be correlated with decrease in aminoaciduria at that time. The study showed a significant correlation between urinary carnitine excretion and serum PTH levels. In our study we did not find any significant difference between the serum total carnitine levels on the first (pre-treatment) and the 15(th) day (posttreatment), and both values were lower than the reference values for the same age group. We observed that the total serum carnitine levels did not change on the 15(th) day of the post-treatment period in spite of a decrease in urinary carnitine excretion. The results of the present study indicated that carnitine metabolism is disturbed in nutritional rickets. Further evaluation of rickets cases and new studies will probably lead to a better understanding of carnitine metabolism in nutritional rickets

Carnitinuria in rickets due to vitamin D deficiency

In this study, we measured the serum-urine total carnitine levels and PTH levels before and after treatment in 18 patients with nutritional rickets. The urine and blood samples were taken on the first (pretreatment) and the 15(th) day of the study (post-treatment). The total carnitine levels of serum and urine somples, serum PTH and serum-urine creatinine concentrations were determined. We found that the levels of carnitine excreted in the mine on the first (pre-treatment) and on the 15(th) day (post-treatment) were higher than the reference levels. Decrease in carnitine excretion on the 15(th) day seemed to be correlated with decrease in aminoaciduria at that time. The study showed a significant correlation between urinary carnitine excretion and serum PTH levels. In our study we did not find any significant difference between the serum total carnitine levels on the first (pre-treatment) and the 15(th) day (posttreatment), and both values were lower than the reference values for the same age group. We observed that the total serum carnitine levels did not change on the 15(th) day of the post-treatment period in spite of a decrease in urinary carnitine excretion. The results of the present study indicated that carnitine metabolism is disturbed in nutritional rickets. Further evaluation of rickets cases and new studies will probably lead to a better understanding of carnitine metabolism in nutritional rickets