Lambrecht A.,Catholic University of Leuven |
Maurey H.,Hopital Bicetre |
Drunat S.,Hopital Robert Debre |
Drunat S.,University of Paris Pantheon Sorbonne |
And 6 more authors.
Molecular Genetics and Metabolism Reports
We report a toddler affected with Angelman syndrome and isovaleric acidemia (IVA). Such association was due to paternal uniparental isodisomy (UPD) of chromosome 15 in which the proband inherited two paternal copies of an IVA gene point mutation. As both diseases may have severe impact on neurodevelopment, adequate treatment of IVA should be discussed. In our patient however, the variant identified likely causes asymptomatic organic aciduria. Such findings emphasize that paternal UPD 15 can rarely lead to co-occurrence of Angelman syndrome and potentially treatable inborn errors of metabolism. © 2015 The Authors. Published by Elsevier Inc. Source
Rebai I.,National Institute Mongi Ben Hmida of Neurology |
Kraoua I.,National Institute Mongi Ben Hmida of Neurology |
Benrhouma H.,National Institute Mongi Ben Hmida of Neurology |
Rouissi A.,National Institute Mongi Ben Hmida of Neurology |
And 3 more authors.
Brain and Development
Lesch Nyhan syndrome (LNS) is an X-linked recessive disorder due to complete deficiency of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. Defect of the enzymatic activity is related to mutations of the HPRT1 gene. The disorder severity is due to neurological features and renal complications. Up to now, more than 300 mutations have been reported. We report on a Tunisian child with a severe phenotype due to a novel identified complex mutation. © 2014 The Japanese Society of Child Neurology. Source
Del Mar Gonzalez-Barroso M.,Laboratory of Metabolic Biochemistry |
Del Mar Gonzalez-Barroso M.,CSIC - Biological Research Center |
De Lonlay P.,University of Paris Descartes |
Ricquier D.,Laboratory of Metabolic Biochemistry |
And 2 more authors.
Frontiers in Diabetes
Glucose-stimulated insulin secretion by pancreatic beta-cells is a highly complex process. Mitochondria play a critical role in the control of this pathway mainly by modulating ATP supply. Reactive oxygen species have also been proposed as metabolic signals in glucose-induced insulin secretion. A partial uncoupling of mitochondrial substrate oxidation from ATP synthesis would decrease insulin secretion. The mitochondrial uncoupling protein UCP2 was firstly considered as a regulator of ATP production in beta-cells by uncoupling oxidative phosphorylation. The mitochondrial proton transporter responsible for heat production by brown adipocyte mitochondria is evolutionarily related to UCP1. Genetic, physiological, and pathological studies suggest that UCP2 is a negative regulator of insulin secretion in rodents and humans. We identified loss-of-function mutations in the UCP2 gene in 2 young patients with congenital hyperinsulinism, making UCP2 a candidate gene for this disease. Functional studies of the mutants confirmed this hypothesis. It has been proposed that UCP2 could attenuate insulin secretion through a dual role in beta-cells by decreasing the ATP/ADP ratio or modulating the production of reactive oxygen species. This chapter describes the proposed implications of UCP2 as a modulator of insulin secretion in beta-cells. The contribution of UCP2 in glucose metabolism and sensing in other cell types is also discussed. © 2012 S. Karger AG, Basel. Source
Boenzi S.,Bambino Gesu Pediatric Hospital |
Rizzo C.,Laboratory of Metabolic Biochemistry |
Di Ciommo V.M.,Unit of Epidemiology and Biostatistics |
Martinelli D.,Bambino Gesu Pediatric Hospital |
And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis
Guanidinoacetate (GAA) and creatine are reliable biochemical markers for primary and secondary creatine defects. We describe a method by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for simultaneous determination of plasma GAA and creatine. We analyzed 283 healthy subjects from 0 to 63 years old to obtain age-related control values. Methods: Plasma samples were extracted with acetonitrile containing 13C2-GAA and d3-creatine. Samples were analyzed by LC-MS/MS in positive ionisation mode, after derivatization to butyl-esters. Optimal chromatographic separation was achieved using a column Supelcosil™ LC-4.6. mm with isocratic elution in 5. min. Results: Run time was 5. min. Standard curves were linear from 0.05 to 200 μmol/L for creatine and from 0.02 to 40 μmol/L for GAA. Limit of detection (LOD) and limit of quantitation (LOQ) were respectively 0.005 and 0.05 μmol/L for creatine; LOD and LOQ were 0.002 and 0.02 μmol/L respectively for GAA. Intra and inter-assay CVs for creatine and GAA were <8%. Recovery experiments adding 50 and 100 μmol/L creatine and 10 and 20 μmol/L GAA were 102.1% and 101.2%, for creatine; 102.95% and 96.45% for GAA. The method was applied to 283 plasma controls from healthy subjects to obtain control values in three specific age ranges: 0-12, 13-20, >20 years old. Conclusion: A rapid and high sensitive LC-MS/MS method was developed and validated for determination of creatine and GAA in plasma and it could also be applied to other biological materials, such as CFS and urines. This method is useful for diagnoses of primary and also for secondary creatine defects that may occur in inherited metabolic diseases in which precursors of creatine biosynthesis are involved. © 2011 Elsevier B.V. Source
Boenzi S.,Laboratory of Metabolic Biochemistry |
Deodato F.,Bambino Gesu Childrens Hospital |
Taurisano R.,Bambino Gesu Childrens Hospital |
Martinelli D.,Bambino Gesu Childrens Hospital |
And 6 more authors.
Clinica Chimica Acta
Two oxysterols, cholestan-3β,5α,6β-triol (C-triol) and 7-ketocholesterol (7-KC), have been recently proposed as diagnostic markers of Niemann-Pick type C (NP-C) disease, representing a potential alternative diagnostic tool to the more invasive and time consuming filipin test in cultured fibroblasts. Usually, the oxysterols are detected and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using atmospheric pressure chemical ionization (APCI) or electro-spray-ionization (ESI) sources, after a variety of derivatization procedures to enhance sensitivity. We developed a sensitive LC-MS/MS method to quantify the oxysterols in plasma as dimethylaminobutyrate ester, suitable for ESI analysis. This method, with an easy liquid-phase extraction and a short derivatization procedure, has been validated to demonstrate specificity, linearity, recovery, lowest limit of quantification, accuracy and precision. The assay was linear over a concentration range of 0.5-200. ng/mL for C-triol and 1.0-200. ng/mL for 7-KC. Intra-day and inter-day coefficients of variation (CV%) were <. 15% for both metabolites. Receiver operating characteristic analysis estimates that the area under curve was 0.998 for C-triol, and 0.972 for 7-KC, implying a significant discriminatory power for the method in this patient population of both oxysterols. In summary, our method provides a simple, rapid and non-invasive diagnostic tool for the biochemical diagnosis of NP-C disease. © 2014 Elsevier B.V. Source