The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Bruce Barshop - One of the best experts on this subject based on the ideXlab platform.
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metabolomic approaches to mitochondrial disease correlation of urine Organic acids
Mitochondrion, 2004Co-Authors: Bruce BarshopAbstract:In order to examine correlations which might be useful in ascertaining or confirming the diagnosis of mitochondrial disease, a retrospective analysis of urine Organic acids was performed. Among 3646 analyses from randomly selected samples referred to our laboratory, there were 258 specimens from 67 patients with various known disorders of mitochondrial oxidative function, most of whom were known to have chronic and persistent elevations of blood lactic acid, and 176 samples from 21 patients with diagnosed Organic Acidemia. Urine lactate was not a useful discriminator; only 7.6% of results from infants with mitochondrial disease fell the 95th percentile for patients without mitochondrial disease. Most of the Krebs cycle intermediates were also not useful in discriminating patients with mitochondrial disorders. Interestingly, there was strikingly poor correlation among most of those analytes in all patient groups, but fumarate and malate were uniquely well correlated (r2 = 0.840). Fumarate and malate were also the most useful in distinguishing patients with mitochondrial disease and Organic Acidemia from the pool of unselected or undiagnosed patients, although the utility was somewhat limited. Using a cutoff value of approximately 90 mmol/mol creatinine for fumarate or malate at age <1 year, or a cutoff of approximately 25 for older patients, 25ndash; 30% of mitochondrial disease patients can be distinguished with a 5% false positive rate. Further refinements to this approach may better characterize the metabolomic profile and may improve the diagnostic utility of quantitative Organic acid analysis in mitochondrial disease.
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Metabolomic approaches to mitochondrial disease: correlation of urine Organic acids.
Mitochondrion, 2004Co-Authors: Bruce BarshopAbstract:In order to examine correlations which might be useful in ascertaining or confirming the diagnosis of mitochondrial disease, a retrospective analysis of urine Organic acids was performed. Among 3646 analyses from randomly selected samples referred to our laboratory, there were 258 specimens from 67 patients with various known disorders of mitochondrial oxidative function, most of whom were known to have chronic and persistent elevations of blood lactic acid, and 176 samples from 21 patients with diagnosed Organic Acidemia. Urine lactate was not a useful discriminator; only 7.6% of results from infants with mitochondrial disease fell the 95th percentile for patients without mitochondrial disease. Most of the Krebs cycle intermediates were also not useful in discriminating patients with mitochondrial disorders. Interestingly, there was strikingly poor correlation among most of those analytes in all patient groups, but fumarate and malate were uniquely well correlated (r2 = 0.840). Fumarate and malate were also the most useful in distinguishing patients with mitochondrial disease and Organic Acidemia from the pool of unselected or undiagnosed patients, although the utility was somewhat limited. Using a cutoff value of approximately 90 mmol/mol creatinine for fumarate or malate at age
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Kearns–Sayre Syndrome Presenting as 2-Oxoadipic Aciduria
Molecular Genetics and Metabolism, 2000Co-Authors: Bruce Barshop, Karen A. Mcgowan, Robert K. Naviaux, Martin Friedlander, William L. Nyhan, Richard H HaasAbstract:Abstract A patient with 2-oxoadipic aciduria and 2-aminoadipic aciduria presented at 2 years of age with manifestations typical of Organic Acidemia, episodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age she developed typical Kearns–Sayre syndrome with complete heart block, retinopathy, and ophthalmoplegia. Southern blot revealed a deletion in the mitochondrial genome.
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3-Hydroxyisobutyric Aciduria: An Inborn Error of Valine Metabolism
Pediatric Research, 1991Co-Authors: William L. Nyhan, Bruce Barshop, Jon Wolff, Lawrence SweetmanAbstract:3-Hydroxyisobutyric aciduria, a disorder of valine metabolism, has been found in a boy in whom the clinical picture was that of a typical Organic Acidemia with repeated episodes of ketoacidosis requiring admission to hospital and parenteral fluid therapy, along with impressive failure to thrive and chronic lactic Acidemia. The excretion of 3-hydroxyisobutyric acid ranged from 170 to 390 mmol/mol of creatinine. The administration of valine increased this to 18 700 mmol/mol of creatinine and reproduced the clinical picture of ketoacidosis. Concentrations of free carnitine were low, and esterified carnitine was elevated. Treatment with carnitine and a diet restricted in protein appeared to be beneficial.
P T Ozand - One of the best experts on this subject based on the ideXlab platform.
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Neurophysiologic correlates of Organic Acidemias: a survey of 107 patients.
Brain & development, 1994Co-Authors: B Stigsby, Z Rahbeeni, S M Yarworth, O Dabbagh, C De Gier Munk, N Abdo, J Brismar, G G Gascon, P T OzandAbstract:The files of 107 patients with 19 different types of Organic Acidemia were reviewed retrospectively. Approximately 50% of the patients had abnormal electroencephalogram (EEG) at the time of initial study. In patients who had serial studies, the EEG deteriorated in 38% and improved in 15%. The predominant EEG abnormality encountered was slowing of the background activity in various degrees. Focal or generalized paroxysmal activity occurring in conjunction with slow background activity indicated a poor prognosis. Brainstem auditory evoked potentials (BAEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP) were analyzed. The VEP was abnormal in 44%, BAEP in 39%, and SEP in 29% of the patients. Given the magnitude and frequency by which neurophysiological abnormalities occur in Organic Acidemias, neurophysiology testing provides complementary functional information and has an important place in the clinical work-up of these diseases.
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CT and MR of the brain in the diagnosis of Organic Acidemias. Experiences from 107 patients.
Brain & development, 1994Co-Authors: J Brismar, P T OzandAbstract:The results of CT and/or MRI of the brain in 107 patients with different types of Organic Acidemia are presented. The CSF spaces were wide in more than two-thirds of the patients, in 46 slightly-to-moderately and in 26 markedly-to-severely dilated. Marked widening of the operculae was found in all 5 patients with glutaric Acidemia type 1, but open opercula was also found in other Organic Acidemias. White matter changes were found in about half the patients, in 28 mildly-to-moderately pronounced, in another 28 marked or severe. Basal ganglia or central pathway pathology was seen in a total of 34 patients, i.e. 32%. These changes in 25 patients involved the caudate and/or lentiform nuclei: in 14 cases the T2 signal was increased and volume loss was present, in 9 cases increased T2 signal with preserved volume was found (in one of these the changes were transient). In 2 patients, both with ethylmalonic aciduria (cause unknown), only small high T2 spots were seen in the caudate heads and the putamina. In 4 patients, all suffering from methylmalonic Acidemia, only the globus pallidus was affected. In 3 patients, all with beta-ketothiolase deficiency, high T2 intensity changes were seen only in the postero-lateral putamina. The remaining 8 patients represent a variety of different locations of lesions. The CT or MRI findings in many patients with Organic Acidemias should alert the radiologist that a neurometabolic disorder may be present; in some cases the location and appearance of the lesions may even suggest the correct diagnosis.
Seiji Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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Clinical study of Organic Acidemias and fatty acid oxidation disorders detected in adults
Rinsho shinkeigaku = Clinical neurology, 2013Co-Authors: Kenji Yamada, Yuki Hasegawa, Yoko Yoshikawa, Tomoo Takahashi, Hironori Kobayashi, Yuichi Mushimoto, Jamiyan Purevsuren, Seiji YamaguchiAbstract:Adult-onset inborn errors of metabolism (IEM) are very rare and their details remain unknown. Diagnosis, age at onset, clinical findings, and outcome of patients with IEM over 20 years old whose diagnosis were made at Shimane University between 2001 and 2010 were investigated. Out of 386 IEM cases identified, 24 cases (6.4%) were diagnosed during adulthood, among which 15 patients were adult onset. There were 11 cases with alkaptonuria, 6 patients with Organic Acidemia without alkaptonuria, 4 cases with urea cycle disorders and 3 subjects with fatty acid oxidation disorders. Outcome of adult-onset IEM are better than those of child-onset; however, some patients suffered from progressive neurological disorders because of the time lag before the diagnosis are determined after the onset. Blood acylcarnitines and urine Organic acids should be analyzed for adult patients with unknown regression or mental retardation for early diagnosis.
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Gas chromatographic-mass spectrometric screening for Organic Acidemias using dried urine filter paper : determination of α-ketoacids
Journal of chromatography. B Biomedical sciences and applications, 2001Co-Authors: Masahiko Kimura, Misako Iga, Seiji YamaguchiAbstract:There are several Organic acid disorders that require information on α-ketoacids, such as maple syrup urine disease or α-ketoadipic Acidemia. The recovery, stability and diagnostic availability of α-ketoacids in dried urine filter paper analyzed by GC–MS with oxime-trimethylsilyl derivatization was studied for Organic Acidemia screening. The recovery of all nine types of α-ketoacids tested, but for phenylpyruvate, 2-ketoadipate, and p-OH-phenylpyruvate, from filter paper samples was acceptable. The stability of pyruvate, branched-chain α-ketoacids, α-ketoadipate and α-ketoglutarate was stable for at least 28 days, although some α-ketoacids such as succinylacetone were unstable. It indicated it was difficult to diagnose only tyrosinemia type 1 among nine specimens from Organic Acidemia patients tested. The method could be applied to global Organic Acidemia screening.
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Simplified screening for Organic Acidemia using GC/MS and dried urine filter paper: a study on neonatal mass screening
Early human development, 2000Co-Authors: Misako Iga, Masahiko Kimura, Seiji YamaguchiAbstract:Abstract A simplified method for Organic Acidemia screening using GC/MS, the urease/direct method, is now available. To establish a practical screening system for Organic Acidemias, we studied the usefulness of dried urine filter paper (filter paper urine) and the application of a personal computer-based system of automated metabolic profiling and interpretation (automated system) that we earlier developed. In a comparison of filter paper urine with liquid urine, creatinine levels ranging from 4.6 to 122.5 mg/dl, showed an excellent correlation (r=0.9554), when the volumes of blotted urine and distilled water soaked were the same. Recovery of all 17 compounds except for citrate was similar between liquid and filter paper urine. CV values of 22 compounds tested ranged from 5.5 to 22.4% in the liquid urine, and from 7.7 to 29.8% in the filter paper urine. The CV values in stable isotope dilution analysis were much smaller in all nine compounds tested. As to the stability of compounds, the percentage changes to values at day 0 were within about ±25% on day 28. We compiled GC/MS data, including methylene unit values, quantifying and confirming ions of 163 different Organic acids and others, to use the automated system. We analyzed specimens from 55 patients with 17 different metabolic disorders. In 54 of the 55 specimens, the correct diagnosis was successfully indicated. Neonatal mass screening for Organic Acidemias warrants ongoing attention using this simplified method and filter paper urine.
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Automated metabolic profiling and interpretation of GC/MS data for Organic Acidemia screening: a personal computer-based system.
The Tohoku journal of experimental medicine, 1999Co-Authors: Masahiko Kimura, Takashi Yamamoto, Seiji YamaguchiAbstract:We have developed a personal computer-based system designed for automated metabolic profiling of urinary Organic acids by gas chromatography-mass spectrometry (GC/MS) and data interpretation for Organic Acidemia screening. For the automated profiling, we compiled retention indices, two target ions and their intensity ratio for 126 urinary metabolites. Metabolites above the cut-off values were flagged as abnormal compounds. The data interpretation was based on combination of the flagged metabolites. Diagnostic or index metabolites were categorized into three groups, “AND,” “OR” and “NO,” and compiled for each disorder to improve the specificity of the diagnosis. Groups “AND” and “OR” comprised essential and optional compounds, respectively, which and both to reach a specific diagnosis. Group “NO” comprised metabolites that must be absent to make a definite diagnosis. We tested this system by analyzing urine specimens from 48 patients previously diagnosed as having Organic Acidemias. In all cases, the diagnostic metabolites were identified and each correct diagnosis could be found among the possible diseases suggested by the system. Hence, with this simplified automated system, more people will be able to participate extensively in any screening programs using GC/MS.
Magdalena Ugarte - One of the best experts on this subject based on the ideXlab platform.
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Prenatal diagnosis of propionic Acidemia.
Prenatal diagnosis, 2004Co-Authors: Celia Pérez-cerdá, Lourdes R. Desviat, Belén Pérez, Begoña Merinero, P. Rodríguez Pombo, Magdalena UgarteAbstract:In this report we summarize our experience in prenatal diagnosis of propionic Acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl-CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this Organic Acidemia.
William L. Nyhan - One of the best experts on this subject based on the ideXlab platform.
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Kearns–Sayre Syndrome Presenting as 2-Oxoadipic Aciduria
Molecular Genetics and Metabolism, 2000Co-Authors: Bruce Barshop, Karen A. Mcgowan, Robert K. Naviaux, Martin Friedlander, William L. Nyhan, Richard H HaasAbstract:Abstract A patient with 2-oxoadipic aciduria and 2-aminoadipic aciduria presented at 2 years of age with manifestations typical of Organic Acidemia, episodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age she developed typical Kearns–Sayre syndrome with complete heart block, retinopathy, and ophthalmoplegia. Southern blot revealed a deletion in the mitochondrial genome.
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Neurologic nonmetabolic presentation of propionic Acidemia.
Archives of neurology, 1999Co-Authors: William L. Nyhan, Carolyn Bay, Elizabeth Webb Beyer, Melissa MaziAbstract:Background Patients with propionic Acidemia usually present in the neonatal period with life-threatening ketoacidosis, often complicated by hyperammonemia. It was thought that the neurologic abnormalities seen in this disease were exclusively the consequences of these acute crises. Experience with 2 patients with propionic Acidemia indicates that this disease may present first with prominent neurologic disease without the life-threatening episodes of ketoacidosis that usually serve as the alerting signals for a diagnosis of an Organic Acidemia. Objective To examine the clinical and metabolic aspects of 2 patients with a phenotype that suggested disease of the basal ganglia. Design Examination of patterns of Organic acids of the urine and enzyme assay for propionyl-CoA carboxylase in fibroblasts and lymphocytes. Setting Referral population to a biochemical genetics laboratory. Patients Two patients whose prominent features were hypotonia followed by spastic quadriparesis and choreoathetosis. Both had seizures. One patient was mildly mentally retarded but grew normally physically. The other had profound mental retardation and failure to thrive; he also self-mutilated his lower lip. Self-injurious behavior has not been reported in this disease. Main Outcome Measures Clinical description, blood ammonia levels, Organic acid levels in the urine, and enzyme activity. Results Excretion of metabolites, including methylcitrate, was typical. Residual activity of propionyl-CoA carboxylase approximated 5% of the control in each patient. Conclusions Propionic Acidemia can present as a pure neurologic disease without acute episodes of massive ketoacidosis. Hyperammonemia may occur after infancy in some patients, presenting as Reye syndrome.
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3-Hydroxyisobutyric Aciduria: An Inborn Error of Valine Metabolism
Pediatric Research, 1991Co-Authors: William L. Nyhan, Bruce Barshop, Jon Wolff, Lawrence SweetmanAbstract:3-Hydroxyisobutyric aciduria, a disorder of valine metabolism, has been found in a boy in whom the clinical picture was that of a typical Organic Acidemia with repeated episodes of ketoacidosis requiring admission to hospital and parenteral fluid therapy, along with impressive failure to thrive and chronic lactic Acidemia. The excretion of 3-hydroxyisobutyric acid ranged from 170 to 390 mmol/mol of creatinine. The administration of valine increased this to 18 700 mmol/mol of creatinine and reproduced the clinical picture of ketoacidosis. Concentrations of free carnitine were low, and esterified carnitine was elevated. Treatment with carnitine and a diet restricted in protein appeared to be beneficial.