Laboratoire Of Biochimie Metabolique

Paris, France

Laboratoire Of Biochimie Metabolique

Paris, France
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Mochel F.,French Institute of Health and Medical Research | Duteil S.,Institute Of Myologie | Duteil S.,French Atomic Energy Commission | Duteil S.,University Pierre and Marie Curie | And 11 more authors.
European Journal of Human Genetics | Year: 2010

We previously identified a systemic metabolic defect associated with early weight loss in patients with Huntington's disease (HD), suggesting a lack of substrates for the Krebs cycle. Dietary anaplerotic therapy with triheptanoin is used in clinical trials to promote energy production in patients with peripheral and brain Krebs cycle deficit, as its metabolites-C5 ketone bodies-cross the blood-brain barrier. We conducted a short-term clinical trial in six HD patients (UHDRS (Unified Huntington Disease Rating Scale)=33±13, 15-49) to monitor the tolerability of triheptanoin. We also assessed peripheral markers of short-term efficacy that were shown to be altered in the early stages of HD, that is, low serum IGF1 and 31P-NMR spectroscopy (NMRS) in muscle. At baseline, 31P-NMRS displayed two patients with end-exercise muscle acidosis despite a low work output. On day 2, the introduction of triheptanoin was well tolerated in all patients, and in particular, there was no evidence of mitochondrial overload from triheptanoin-derived metabolites. After 4 days of triheptanoin-enriched diet, muscle pH regulation was normalized in the two patients with pretreatment metabolic abnormalities. A significant increase in serum IGF1 was also observed in all patients (205±60 ng/ml versus 246±68 ng/ml, P=0.010). This study provides a rationale for extending our anaplerotic approach with triheptanoin in HD. © 2010 Macmillan Publishers Limited All rights reserved.


Nadaud S.,French Institute of Health and Medical Research | Nadaud S.,University Pierre and Marie Curie | Nadaud S.,ICAN Institute for Cardiometabolism and Nutrition | Poirier O.,French Institute of Health and Medical Research | And 21 more authors.
European Journal of Clinical Investigation | Year: 2013

Background: The various aetiologies and risk factors for pulmonary arterial hypertension (PAH) lead to close phenotypes with small differences. Plasma microparticles have been shown to be increased in vascular pathologies including PAH. The aim of this study was to determine whether the levels of endothelial and platelet-derived microparticles could vary between different forms of PAH: idiopathic PAH (iPAH), heritable PAH associated with BMPR2 (Bone morphogenetic protein receptor, type II) mutation (hPAH) and PAH associated with connective tissue diseases (aPAH). Materials and methods: Microparticles were analysed using flow cytometry in plasma from controls and iPAH, hPAH and aPAH patients. Platelet-derived MP (PMP) were defined as CD31+/CD41+ and endothelial-derived MP (EMP) as CD31+/CD41-. Two populations of PMP were isolated according to their size, defining small PMP (0·3-0·5μm) and large PMP (0·5-0·9μm). BMPR2 genotype, clinical and biologic parameters were recorded. Results: EMP and small PMP levels in iPAH, hPAH and aPAH were similar and were significantly increased as compared with controls. No differences in large PMP levels were observed. After adjusting for age, sex, proBNP and CRP, EMP and small PMP levels did not correlate with clinical parameters. Conclusions: iPAH, hPAH and aPAH were characterized by increased levels of EMP and of small PMP, a new class of PMP which seems to be differentially produced than large PMP. © 2012 Stichting European Society for Clinical Investigation Journal Foundation.


Feillet F.,French Institute of Health and Medical Research | Garnotel R.,Laboratoire Of Biologie Et Of Recherche Pediatrique | Jeannesson E.,French Institute of Health and Medical Research | Vassault A.,Laboratoire Of Biochimie Metabolique
Archives de Pediatrie | Year: 2012

MCAD deficiency is the most common fatty acid oxidation disorder, with the prevalence varying from 1/10,000 to 1/27,000 in the countries adjacent to France. As the High Authority for Health has recently proposed including MCAD deficiency in the panel of diseases neonatally screened for in France, a consensus was written for the management of MCAD deficiency diagnosed either clinically or by neonatal screening. Patients may present acutely with hyperammonemia, hypoglycemia, encephalopathy, and hepatomegaly, mainly after a prolonged fast of intercurrent infection. Sudden death related to heartbeat disorders may also occur. The diagnosis of MCAD deficiency is suspected on the plasma acylcarnitine and/or the urinary organic acid profile. The diagnosis is confirmed by molecular biology and the enzymatic activity for patients who are not homozygous for the main mutation c.985A>G. However, some MCAD-deficient individuals may remain asymptomatic throughout life. The mainstay of treatment consists in avoiding prolonged fast and prescribing l-carnitine for patients who exhibit a deficiency in plasma carnitine. This management has radically modified the natural history of MCAD deficiency. This consensus will allow homogeneous management of these patients once the neonatal screening of MCAD deficiency has been introduced in France. © 2011 Elsevier Masson SAS.


Degos B.,Hopital Pitie Salpetriere | Degos B.,University Pierre and Marie Curie | Laforet P.,Institute Of Myologie | Jardel C.,Laboratoire Of Biochimie Metabolique | And 9 more authors.
Journal of Clinical Neuroscience | Year: 2014

Recent experimental data underline the relationship between mitochondria and immune function. Clinical reports of patients presenting with mitochondrial dysfunction associated with dysimmune responses in the central nervous system reinforce this new concept. We describe the first case of a woman presenting with symptoms related to a novel compound heterozygous mutation of the mitochondrial polymerase γ (POLG) gene, associated with neurological events suggestive of a demyelinating process. Clinical examination revealed bilateral ptosis, progressive external ophthalmoplegia and axonal sensitive polyneuropathy suggestive of a mitochondrial disease. In line with this, muscle biopsy showed ragged red fibers, and sequencing of POLG revealed two heterozygous mutations. In addition, the patient exhibited relapsing neurological symptoms, and cerebral and spinal MRI mimicking multiple sclerosis. This patient stresses the relationship between mitochondrial dysfunction and inflammation. Recent studies suggest that targeting mitochondrial dysfunction could provide benefits in treating some inflammatory diseases. © 2013 Elsevier Ltd. All rights reserved.


Wils J.,University of Rouen | Wils J.,Groupe de veille Guidelines et EBLM de la Societe francaise de biologie clinique SFBC | Fonfrede M.,Laboratoire Of Biochimie Metabolique | Fonfrede M.,Groupe de veille Guidelines et EBLM de la Societe francaise de biologie clinique SFBC | And 4 more authors.
Annales de biologie clinique | Year: 2014

Several tools are available to help evaluate the quality of clinical practice guidelines (CPG). The AGREE instrument (Appraisal of guidelines for research & evaluation) is the most consensual tool but it has been designed to assess CPG methodology only. The European federation of laboratory medicine (EFLM) recently designed a check-list dedicated to laboratory medicine which is supposed to be comprehensive and which therefore makes it possible to evaluate more thoroughly the quality of CPG in laboratory medicine. In the present work we test the comprehensiveness of this check-list on a sample of CPG written in French and published in Annales de biologie clinique (ABC). Thus we show that some work remains to be achieved before a truly comprehensive check-list is designed. We also show that there is some room for improvement for the CPG published in ABC, for example regarding the fact that some of these CPG do not provide any information about allowed durations of transport and of storage of biological samples before analysis, or about standards of minimal analytical performance, or about the sensitivities or the specificities of the recommended tests.


Wils J.,University of Rouen | Wils J.,Groupe de Veille Guidelines et EBLM de la Societe Francaise de Biologie Clinique | FonfrEde M.,Laboratoire Of Biochimie Metabolique | FonfrEde M.,Groupe de Veille Guidelines et EBLM de la Societe Francaise de Biologie Clinique | And 4 more authors.
Annales de Biologie Clinique | Year: 2014

Several tools are available to help evaluate the quality of clinical practice guidelines (CPG). The AGREE instrument (Appraisal of guidelines for research & evaluation) is the most consensual tool but it has been designed to assess CPG methodology only. The European federation of laboratory medicine (EFLM) recently designed a check-list dedicated to laboratory medicine which is supposed to be comprehensive and which therefore makes it possible to evaluate more thoroughly the quality of CPG in laboratory medicine. In the present work we test the comprehensiveness of this check-list on a sample of CPG written in French and published in Annales de biologie clinique (ABC). Thus we show that some work remains to be achieved before a truly comprehensive check-list is designed. We also show that there is some room for improvement for the CPG published in ABC, for example regarding the fact that some of these CPG do not provide any information about allowed durations of transport and of storage of biological samples before analysis, or about standards of minimal analytical performance, or about the sensitivities or the specificities of the recommended tests.


Jday-Daly I.,Laboratoire Of Biochimie Generale | Augereau-Vacher C.,Laboratoire Of Biochimie | De Curraize C.,Laboratoire Of Biochimie Metabolique | Fonfrede M.,Laboratoire Of Biochimie Metabolique | And 3 more authors.
Annales de Biologie Clinique | Year: 2011

As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood glucose monitoring systems (BGMSs) (Optium Xceed (Abbott), Contour TS (Bayer), One Touch Ultra (Lifescan), Stat Strip Xpress (Nova) and Accu Check (Roche) and an evaluation of their sensitivity to changes in hematocrit were conducted in 4 hospitals of Paris. In terms of inaccuracy, all BGMSs have submitted CV repetability under the limits of acceptability. One BGMS (Lifescan) presented a CV of reproducibility outside limit of acceptability (13.1%). The inaccuracy was measured by a comparison method on multiparameter analyser relative to the hexokinase method for two sites, the glucose oxidase for the two others. The coefficients of correlation varied from 0.8405 to 0.9303. However, according to both defined acceptability criteria (absolute value difference between the result acquired on analyzer and those determined with the BGMS), the percentage of results outside acceptability was above 20% for two BGMSs (Abbott and Lifescan). Similarly, a net effect of changes in hematocrit was observed on the results of those two BGMSs.BGMSNovawas the most reliable, because of the correction device for hematocrit and blank substractions owed to interferences. In terms of expertise, BGMSs Nova and Roche have been selected with the best analytical performance and practicability satisfactory. In the future, accreditation with standard NF/EN 22870 requested for point of care testing, will require a close collaboration between biologists and clinicians to establish a system of strict quality control to detect deviations of these BGMSs.


PubMed | Laboratoire Of Biochimie Metabolique, Institute Of Myologie, Center Hospitalier National dOphtalmologie des Quinze Vingts, University Pierre and Marie Curie and 2 more.
Type: Case Reports | Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia | Year: 2013

Recent experimental data underline the relationship between mitochondria and immune function. Clinical reports of patients presenting with mitochondrial dysfunction associated with dysimmune responses in the central nervous system reinforce this new concept. We describe the first case of a woman presenting with symptoms related to a novel compound heterozygous mutation of the mitochondrial polymerase (POLG) gene, associated with neurological events suggestive of a demyelinating process. Clinical examination revealed bilateral ptosis, progressive external ophthalmoplegia and axonal sensitive polyneuropathy suggestive of a mitochondrial disease. In line with this, muscle biopsy showed ragged red fibers, and sequencing of POLG revealed two heterozygous mutations. In addition, the patient exhibited relapsing neurological symptoms, and cerebral and spinal MRI mimicking multiple sclerosis. This patient stresses the relationship between mitochondrial dysfunction and inflammation. Recent studies suggest that targeting mitochondrial dysfunction could provide benefits in treating some inflammatory diseases.


Lussey-Lepoutre C.,French Institute of Health and Medical Research | Lussey-Lepoutre C.,University of Paris Descartes | Bellucci A.,French Institute of Health and Medical Research | Bellucci A.,University of Paris Descartes | And 36 more authors.
Clinical Cancer Research | Year: 2016

Purpose: Germline mutations in genes encoding mitochondrial succinate dehydrogenase (SDH) are found in patients with paragangliomas, pheochromocytomas, gastrointestinal stromal tumors, and renal cancers. SDH inactivation leads to a massive accumulation of succinate, acting as an oncometabolite and which levels, assessed on surgically resected tissue are a highly specific biomarker of SDHx-mutated tumors. The aim of this study was to address the feasibility of detecting succinate in vivo by magnetic resonance spectroscopy. Experimental Design: A pulsed proton magnetic resonance spectroscopy (1H-MRS) sequence was developed, optimized, and applied to image nude mice grafted with Sdhb-/- or wild-type chromaffin cells. The method was then applied to patients with paraganglioma carrying (n = 5) or not (n = 4) an SDHx gene mutation. Following surgery, succinate was measured using gas chromatography/mass spectrometry, andSDHprotein expression was assessed by immunohistochemistry in resected tumors. Results: A succinate peak was observed at 2.44 ppm by 1H-MRS in all Sdhb-/--derived tumors in mice and in all paragangliomas of patients carrying an SDHx gene mutation, but neither in wildtype mouse tumors nor in patients exempt of SDHx mutation. In one patient, 1H-MRS results led to the identification of an unsuspected SDHA gene mutation. In another case, it helped define the pathogenicity of a variant of unknown significance in the SDHB gene. Conclusions: Detection of succinate by 1H-MRS is a highly specific and sensitive hallmark of SDHx mutations. This noninvasive approach is a simple and robust method allowing in vivo detection of the major biomarker of SDHx-mutated tumors. © 2015 American Association for Cancer Research.

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