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: 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

Resistin levels in preterms: are they influenced by fetal inflammatory course?

WOS: 000287728400006PubMed: 20689515Objective: Many different factors are involved in the pathogenesis of preterm deliveries and among them maternal or perinatal infections and inflammatory response have the major role. Researches were carried out about resistin, which is thought to have a role in inflammatory cytokine cycle and it was shown to be associated with growth in neonates. However, no research has been carried out showing its relationship with inflammation in neonates. In this study, we aimed to evaluate the resistin levels in premature neonates and the effect of events such as preterm prelabour rupture of the membranes (PPROMs) and the use of antenatal steroids on these levels. Study Design: The study included 118 preterm neonates. Their medical data together with their mothers' were recorded. Serum resistin levels together with interleukin (IL)-6, C-reactive protein (CRP) and procalcitonin were evaluated in the first 2 h of life. Result: Mean gestational age and birth weight of babies included in the study were 29.6 +/- 2.7 weeks and 1306.4 +/- 393.4 g, respectively. Babies with PPROMs had significantly higher levels of resistin ((n = 30); 70.7 (7.8 to 568.4) ng ml(-1)) than babies without PPROM ((n = 88); 25.9 (5.5 to 528.9) ng ml(-1)) (P = 0.005), and the babies of mothers who received antenatal steroids had significantly lower resistin levels ((n = 44); 20.8 (5.5 to 159.9) ng ml(-1)) than the babies of mothers who did not ((n = 66); 34.6 (7.2 to 568.4) ng ml(-1)) (P = 0.015). There were significant correlations between resistin and IL-6 levels and between IL-6 and procalcitonin and CRP levels in babies whose mothers did not receive antenatal steroids. However, no correlation was found between these parameters in babies whose mothers received antenatal steroids. Conclusion: Preterm delivery and PPROM involve complex cascade of events including inflammation, and steroids are potent anti-inflammatory agents. Elevated resistin levels in babies with PPROM and suppressed levels in babies whose mothers received antenatal steroids reported in this study might have been observed as a result of the effects of fetal inflammation on resistin levels. Journal of Perinatology (2011) 31, 171-175; doi:10.1038/jp.2010.103; published online 5 August 2010Mother and Child Health FoundationMother and Child Health FoundationThis study was supported by the Mother and Child Health Foundation

RESISTIN LEVELS IN PRETERMS: DO THEY INFLUENCE FETAL INFLAMMATORY COURSE?

WOS: 000269862100388

Serum leptin levels and their relationship to tumor necrosis factor-alpha and interleukin-6 in neonatal sepsis

WOS: 000187795000012PubMed: 14714752Circulating leptin concentrations are raised in animal models of inflammation and sepsis and leptin production is also increased in rodents by administration of endotoxin or cytokines. The purpose of this study was to investigate the effect of sepsis on serum leptin concentration and whether circulating leptin was related to tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release in newborn infants. Plasma leptin, TNF-alpha and IL-6 were measured in 20 neonates with culture-proven sepsis as soon as sepsis was diagnosed and after recovery and in 15 healthy control infants. There was no significant difference in plasma leptin levels between septic and control infants (p >0.05); there was also no difference in plasma leptin levels in septic neonates before and after therapy (p >0.05). No relationship between leptin and TNF-alpha (r = 0.16, p >0.05) or II-6 (r = 0.12, p >0.05) was identified. These findings suggest that a major role of leptin in acute neonatal sepsis appears unlikely

A novel mutation which causes a frameshift in the PHOX2B gene causes Haddad syndrome

PubMed: 32073407[No abstract available

VACTERL-H associated with central hypothyroidism: A case report

WOS: 000250607400009PubMed: 18019375VACTERL-H associated with central hypothyroidism: A case report: The VACTERL-14 syndrome is a rare combination of vertebral anomalies, anal atresia, congenital heart defects, tracheo-esophageal fistula, abnormalities of kidneys and limb anomalies together with hydrocephalus. This condition is recognized as a hereditary entity with poor prognosis. We present a newborn weighing 3400 g, born by cesarean section to a 27 years old mother who had had an irregular antenatal follow-up. The patient had severe hydrocephalus, proximal esophageal atresia and distal tracheoesophageal fistula, gastric outlet obstruction, imperforated anus and recto-urethral fistula, patent ductus arterious, a bifid scrotum, a vertebral defect, sacral dimple and central hypothyroidism. The patient had no limb defects. The association of central hypothyroidism and VACTER-L-H has previously not been reported