Publications (13)40.21 Total impact
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Article: Methylation metabolites in amniotic fluid depend on gestational age.
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ABSTRACT: OBJECTIVE: Methylation metabolism is essential for fetus development. However, normative data for amniotic fluid (AF) concentrations of methylation metabolites at different gestational ages are lacking. We aimed to determine in AF reference values of 14 intermediates involved in methylation. METHODS: 268 AFs sampled between 14 and 39 weeks of gestation (WG) were retrospectively selected in our AF bank. Next, we measured methionine-cycle intermediates (S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), total homocysteine, methionine, methyl malonic acid) and methyldonors and methylacceptors (betaine, dimethylglycine, sarcosine, free and total choline, free and total ethanolamine, creatine, guanidinoacetate) by liquid chromatography coupled with tandem mass spectrometry. RESULTS: Reference ranges according to gestational age were determined for each parameter. Strong correlations between metabolites directly connected in their metabolic pathway and between total homocysteine and betaine were observed. CONCLUSION: Methionine, an essential amino-acid required for protein synthesis is the only parameter that dramatically decreases with gestational age. The AdoMet/AdoHcy ratio exponentially increases from 25 WG, which could reflect increasing methylation capacities. The negative correlation between betaine and total homocysteine together with a constant betaine to dimethylglycine ratio during gestation suggest that betaine may be used as a methyl-donor during fetal life. This article is protected by copyright. All rights reserved.Prenatal Diagnosis 04/2013; · 2.11 Impact Factor -
Article: Phosphoethanolamine normal range in pediatric urines for hypophosphatasia screening.
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ABSTRACT: No abstract available.Clinical Chemistry and Laboratory Medicine 06/2012; · 2.15 Impact Factor -
Article: Measurement of free and total sialic acid by isotopic dilution liquid chromatography tandem mass spectrometry method.
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ABSTRACT: The measurement of urine sialic acid (N Acetylneuraminic Acid: Neu5Ac) is useful for screening sialic acid storage disorders. We developed a new LC MS/MS method for the determination of a sialic acid. Urine samples were analyzed, after an HCl n-Butanol derivatization step, by a reverse phase based high-performance liquid chromatography method using 1,2,3-(13)C(3) N-Acetyl-D-neuraminic Acid ((13)C-Neu5Ac) as an internal standard. Selective detection was performed by tandem mass spectrometry using an electrospray source operating in positive ionization mode employing multiple reactions monitoring to monitor N-Acetylneuraminic Acid and the internal standard. The transitions m/z 366→330 and 369→333 for Neu5Ac and (13)C-Neu5Ac were respectively monitored. The limit of the method quantification was 1.40 μM of N-Acetylneuraminic Acid and the calibration curve showed a good linearity up to 1000 μM. The within assay precision and accuracy of the method ranged from 3.22 to 5.95% and 98.69 to 109.18%, respectively and the between assay precision and accuracy ranged, respectively, from 5.15 to 7.65% and 96.14 to 102.30%. The method can be applied for the determination of N-Acetylneuraminic Acid concentrations in urine and other biological fluids (e.g., amniotic and peritoneal fluids).Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 12/2011; 879(31):3694-9. · 2.78 Impact Factor -
Article: Subacute myopathy in a mature patient due to multiple acyl-coenzyme A dehydrogenase deficiency.
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ABSTRACT: Multiple acyl-coenzyme A dehydrogenase deficiency (MADD), also called glutaric aciduria type II, is an inherited metabolic disorder resulting from a deficiency in electron transfer flavoprotein (ETF) or of its ubiquinone oxidoreductase (ETF-QO). It usually occurs in the neonatal period or in early infancy and, very rarely, in adolescents and young adult patients. We report the case of a 55-year-old woman who developed a painful subacute myopathy. Lipid accumulation was found at biopsy. MADD was confirmed by plasma acylcarnitine profile and by assessment of ETF-QO activity in muscle. This study demonstrates that metabolic myopathies usually found in infancy may be also diagnosed in older patients. MADD may be easily treated by riboflavin and coenzyme Q10 and therefore should be included in the differential diagnosis of adult-onset painful myopathy.Muscle & Nerve 03/2011; 43(3):444-6. · 2.37 Impact Factor -
Article: Fatal heart failure associated with CoQ10 and multiple OXPHOS deficiency in a child with propionic acidemia.
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ABSTRACT: The role of a secondary respiratory chain deficiency as an additional mechanism to intoxication, leading to development of long-term energy-dependent complications, has been recently suggested in patients with propionic acidemia (PA). We show for the first time a coenzyme Q(10) (CoQ(10)) functional defect accompanied by a multiple organ oxidative phosphorylation (OXPHOS) deficiency in a child who succumbed to acute heart failure in the absence of metabolic stress. Quinone-dependent activities in the liver (complex I+III, complex II+III) were reduced, suggesting a decrease in electron transfer related to the quinone pool. The restoration of complex II+III activity after addition of exogenous ubiquinone to the assay system suggests CoQ(10) deficiency. Nevertheless, we disposed of insufficient material to perform direct measurement of CoQ(10) content in the patient's liver. Death occurred before biochemical diagnosis of OXPHOS deficiency could be made. However, this case highlights the usefulness of rapidly identifying CoQ(10) defects secondary to PA since this OXPHOS disorder has a good treatment response which could improve heart complications or prevent their appearance. Nevertheless, further studies will be necessary to determine whether CoQ(10) treatment can be useful in PA complications linked to CoQ(10) deficiency.Mitochondrion 02/2011; 11(3):533-6. · 3.62 Impact Factor -
Article: Post-mortem MRI reveals CPT2 deficiency after sudden infant death.
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ABSTRACT: Inherited metabolic disorders are the cause of a small but significant number of sudden infant deaths in infants. We report on a boy who suddenly died at 10 months of age during an acute illness. Parents declined autopsy; nevertheless, they accepted a whole body MRI, which revealed hepatomegaly with steatosis. Acylcarnitine profile of a blood sample from neonatal Guthrie screening led to the diagnosis of type 2 carnitine palmitoyltransferase deficiency. To conclude, whole body MRI is useful in the investigation of some inherited metabolic causes of sudden infant death, which might prevent future deaths in the family. It is a good alternative when autopsy is refused.European Journal of Pediatrics 12/2010; 169(12):1561-3. · 1.88 Impact Factor -
Article: Coenzyme Q10 is frequently reduced in muscle of patients with mitochondrial myopathy.
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ABSTRACT: Coenzyme Q(10) (CoQ(10)) deficiency has been associated with an increasing number of clinical phenotypes. Whereas primary CoQ(10) defects are related to mutations in ubiquinone biosynthetic genes, which are now being unraveled, and respond well to CoQ(10) supplementation, the etiologies, and clinical phenotypes related to secondary deficiencies are largely unknown. The purpose of this multicenter study was to evaluate the frequency of muscle CoQ(10) deficiency in a cohort of 76 patients presenting with clinically heterogeneous mitochondrial phenotypes which included myopathy among their clinical features. A reliable diagnostic tool based on HPLC quantification was employed to measure muscle CoQ(10) levels. A significant proportion of these patients (28 over 76) displayed CoQ(10) deficiency that was clearly secondary in nine patients, who harbored a pathogenic mutation of mitochondrial DNA. This study provides a rationale for future therapeutic trials on the effect of CoQ(10) supplementation in patients with mitochondrial diseases presenting with myopathy among clinical features.Neuromuscular Disorders 11/2009; 20(1):44-8. · 2.80 Impact Factor -
Article: Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-Coenzyme A dehydrogenase (VLCAD) deficiency.
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ABSTRACT: Very Long-Chain Acyl-CoA dehydrogenase (VLCAD) deficiency is an inborn error of mitochondrial long-chain fatty acid oxidation (FAO) most often occurring in childhood with cardiac or liver involvement, but rhabdomyolysis attacks have also been reported in adults. We report in this study the clinical, biochemical and molecular studies in 13 adult patients from 10 different families with VLCAD deficiency. The enzyme defect was demonstrated in cultured skin fibroblasts or lymphocytes. All patients exhibited exercise intolerance and recurrent rhabdomyolysis episodes, which were generally triggered by strenuous exercise, fasting, cold or fever (mean age at onset: 10 years). Inaugural life-threatening general manifestations also occurred before the age of 3 years in four patients. Increased levels of long-chain acylcarnitines with tetradecenoylcarnitine (C14:1) as the most prominent species were observed in all patients. Muscle biopsies showed a mild lipidosis in four patients. For all patients but two, molecular analysis showed homozygous (4 patients) or compound heterozygous genotype (7 patients). For the two remaining patients, only one mutation in a heterozygous state was detected. This study confirms that VLCAD deficiency, although being less frequent than CPT II deficiency, should be systematically considered in the differential diagnosis of exercise-induced rhabdomyolysis. Measurement of fasting blood acylcarnitines by tandem mass spectrometry allows accurate biochemical diagnosis and should therefore be performed in all patients presenting with unexplained muscle exercise intolerance or rhabdomyolysis.Neuromuscular Disorders 04/2009; 19(5):324-9. · 2.80 Impact Factor -
Article: Characterization of insulin secretion and resistance in type 2 diabetes of adolescents.
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ABSTRACT: Type 2 diabetes (T2D) in obese children is an emerging problem, including in Europe. Its presentation at diagnosis very often differs from that in adults. The objective of this study was to investigate the relative contributions of the two components of T2D, insulin resistance and insulin secretion, early in the history of the disease in adolescents. Six obese adolescents with T2D were included 2 months to 4.3 yr after diagnosis (five girls and one boy; median age, 15.4 yr; median body mass index, 4.4 sd). Peripheral and hepatic insulin sensitivity was evaluated with euglycemic hyperinsulinemic (40 mU/m(2).min) clamp. First-phase insulin release was evaluated after iv glucose stimulation. A graded iv glucose infusion and an arginine test were performed to measure insulin secretion. All patients showed decreased peripheral glucose uptake to the same extent. Five patients showed hepatic insulin resistance. First-phase insulin release was very low in two patients. Three patients showed an exaggerated insulin response under graded glucose infusion and preserved secretion under arginine stimulation. Three other patients, with elevated fasting plasma glucose levels, demonstrated a very low insulin response under glucose stimulation and a low insulin response under arginine stimulation. These data emphasize that together with marked insulin resistance, the failure of beta-cell function is a major component in the course of T2D in childhood.Journal of Clinical Endocrinology & Metabolism 03/2006; 91(2):401-4. · 6.50 Impact Factor -
Article: Detection of 28 neurotransmitters and related compounds in biological fluids by liquid chromatography/tandem mass spectrometry.
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ABSTRACT: This work presents two liquid chromatography/tandem mass spectrometry (LC/MS/MS) acquisition modes: multiple reaction monitoring (MRM) and neutral loss scan (NL), for the analysis of 28 compounds in a mixture. This mixture includes 21 compounds related to the metabolism of three amino acids: tyrosine, tryptophan and glutamic acid, two pterins and five deuterated compounds used as internal standards. The identification of compounds is achieved using the retention times (RT) and the characteristic fragmentations of ionized compounds. The acquisition modes used for the detection of characteristic ions turned out to be complementary: the identification of expected compounds only is feasible by MRM while expected and unexpected compounds are detected by NL. In the first part of this work, the fragmentations characterizing each molecule of interest are described. These fragmentations are used in the second part for the detection by MRM and NL of selected compounds in mixture with and without biological fluids. Any preliminary extraction precedes the analysis of compounds in biological fluids.Rapid Communications in Mass Spectrometry 02/2006; 20(9):1405-21. · 2.79 Impact Factor -
Article: Differences in coenzyme Q10 content in deltoid and quadriceps muscles.
Clinica Chimica Acta 04/2003; 329(1-2):147-8. · 2.54 Impact Factor -
Article: Cerebrospinal fluid lactate and pyruvate concentrations and their ratio in children: age-related reference intervals.
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ABSTRACT: Lactate (L) and pyruvate (P) concentrations in cerebrospinal fluid (CSF) and the L/P ratio have diagnostic value in numerous primary and acquired disorders affecting the central nervous system, but age-related reference values are not available for children. We analyzed CSF and blood lactate and pyruvate concentrations and their ratio in a 4-year retrospective survey of a children's hospital laboratory database. Reference intervals (10th-90th percentiles) were established from data on 197 hospitalized children. A recent regression modeling method was used to normalize and smooth values against age. The model equation of best fit was calculated for each variable. Slight age-related variations were shown by the model, with an increase in lactate, a decrease in pyruvate, and a resulting increase in the L/P ratio with increasing age. However, the SD did not vary with age. We defined the upper limit of the reference intervals as the 90th percentiles, which from birth to 186 months of age varied continuously from 1.78 to 1.88 mmol/L (6%), 148 to 139 micro mol/L (6%), and 16.9 to 19.2 (14%) for lactate, pyruvate, and the L/P ratio, respectively. At a threshold of 2 (in Z-score units), the sensitivity for a subgroup of inborn errors of metabolism (respiratory chain disorders) was 73%, 42%, and 31% for lactate, pyruvate, and the L/P ratio, respectively. In children, CSF lactate and pyruvate concentrations and their ratio appear to vary slightly with age. Average 90th percentile values of 1.8 mmol/L, 147 micro mol/L, and 17, respectively, could be used in infants up to 24 months of age. In older children, age-adjusted reference intervals should be used, especially when values are close to the 90th percentile.Clinical Chemistry 04/2003; 49(3):487-94. · 7.91 Impact Factor -
Article: An enzyme-linked immunoassay for the measurement of rat α1-acid glycoprotein synthesized by cultured hepatocytes
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ABSTRACT: We have developed a sandwich ELISA to quantigy rat α1-acid glycoprotein (AGP). The assay correlated well with RID and the minimum detectable concentration was 1 μg/1. The assay permits high sensitivity determinations of the rate of synthesis of AGP in vitro. The maximum mean rates observed were 1500 and 1800 ng/24 h/106 cells for hepatocytes cultured alone and co-cultured hepatocytes respectively and 39 ng/h/106 cells for isolated hepatocytes.Journal of Immunological Methods.
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2011
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Hôpital universitaire Robert-Debré
Paris, Ile-de-France, France
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