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Biomedical subjects

C Jakobs

Publications and source records attributed to C Jakobs.

At least 307 records · Page 17Linked to original sources
PubMed1989

Determination of plasma bile acids by capillary gas-liquid chromatography-electron capture negative chemical ionization mass fragmentography.

Combined capillary gas-liquid chromatography-electron capture negative chemical ionization mass spectrometry of pentafluorobenzyl ester-TMSi ether derivatives of bile acids and isotope dilution using deuterated internal standards are introduced as a sensitive and selective analysis technique for plasma bile acids. As a result of the high ionization efficiency of pentafluorobenzyl derivatives under electron capturing conditions and minimal fragmentation, the detection limit of this technique is low: 1 pg for each bile acid. The high sensitivity enabled the detection and quantitation of atypical bile acids in 200-microliters aliquots of plasma from fasting healthy adults as exemplified by trihydroxycoprostanic acid (0.002 +/- 0.001 mumol/l) and dihydroxycoprostanic acid (0.013 +/- 0.002 mumol/l).

Adult↗
PubMed1988

Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I.

A sensitive and accurate isotope dilution assay using electron capture negative ion mass fragmentography was developed for succinylacetone in amniotic fluid, plasma and urine. The method utilizes (D4)-5(3)-methyl-3(5)-isoxasole propionic acid as internal standard. Sample pretreatment consisted of oximation at pH less than 2 to 5(3)-methyl-3(5)-isoxasole propionic acid, clean up using liquid partition chromatography and further derivatization to the pentafluorobenzyl ester. Control values in plasma revealed a mean means = 0.044 mumol/l, range = 0.005-0.163 mumol/l, in urine means = 0.15 mumol/l, range 0.01-0.40 mumol/l corresponding to means = 0.03 mumol/mmol creat., range 0.01-0.14 mumol/mmol creat., and in amniotic fluid means = 0.016 mumol/l, range = 0.001-0.030 mumol/l. The utility of the method was demonstrated by quantification of succinylacetone in urine from patients with hereditary tyrosinemia type I (n = 8, excretion range 2.60-493.3 mumol/l corresponding to 0.67-197.3 mumol/mmol creat.) and in two amniotic fluid samples from fetuses affected with this disorder (concentration of succinylacetone 0.085 and 1.50 mumol/l, respectively). Maternal urine from a woman carrying an affected fetus did not show elevated urinary succinylacetone excretion.

Amino Acid Metabolism, Inborn Errors↗
PubMed1987

Stable isotope dilution analysis of pipecolic acid in cerebrospinal fluid, plasma, urine and amniotic fluid using electron capture negative ion mass fragmentography.

A sensitive and accurate stable isotope dilution assay was developed for the measurement of pipecolic acid in body fluids using electron capture negative ion mass fragmentography. The method utilizes [2H11]pipecolic acid as the internal standard. Sample preparation consisted of derivatization in aqueous solution (pH 11.5) of the amine moiety with methyl chloroformate to the N-methylcarbamate, followed by acidic ethyl acetate extraction (pH 2) and further derivatization of the carboxyl moiety to the pentafluorobenzyl ester. Normal values have been determined in cerebrospinal fluid (mean means = 0.041 mumol/l, range 0.010-0.120 mumol/l), in plasma of at term infants (age less than 1 wk, means = 5.73 mumol/l, range 3.75-10.8 mumol/l; age greater than 1 wk, means = 1.46 mumol/l, range 0.70-2.46 mumol/l), in urine of at term infants (age less than 6 mth, means = 32.5 mumol/g. creat., range 9.81-84.5 mumol/g. creat; age greater than 6 mth, means = 6.35 mumol/g. creat., range 0.15-13.6 mumol/g. creat.) and in amniotic fluid (means = 4.65 mumol/l, range 2.24-8.40 mumol/l). The utility of the method was demonstrated for the pipecolic acid quantification in these biofluids of patients with peroxisomal disorders. As affected fetuses with infantile Refsum's disease and Zellweger syndrome showed no significant elevation of pipecolic acid in their surrounding amniotic fluids, the measurement of pipecolic acid in amniotic fluid seemed not to be useful for prenatal diagnosis in these disorders.

Adult↗
PubMed1987

Amniotic fluid propionylcarnitine in methylmalonic aciduria.

Amniotic fluid samples from pregnancies complicated by foetal methylmalonic aciduria and from metabolically normal pregnancies were obtained at 16-18 weeks of gestation and analysed for total, free and acylcarnitine and individual carnitine esters. The amniotic fluid concentrations of total acylcarnitine and propionylcarnitine were higher in pregnancies with higher in pregnancies with methylmalonic aciduria than in normal pregnancies. The predominant carnitine ester was propionylcarnitine in the methylmalonic aciduria group and acetylcarnitine in the normal group. These findings suggest that in methylmalonic aciduria, abnormalities of carnitine metabolism already occur early in gestation. The amount of propionylcarnitine in amniotic fluid may be useful as an additional indicator of foetal methylmalonic aciduria.

Acetylcarnitine↗
PubMed1987

Hyperketotic states due to inherited defects of ketolysis.

From the description of 2 unrelated patients with succinyl-CoA transferase (3-OAT) deficiency and 1 patient with acetoacetyl-CoA thiolase (AAT) deficiency, we have attempted to draw the clinical and metabolic consequences of such defects. The association of recurrent attacks of severe ketoacidosis with blood glucose levels generally high or normal, low lactacidemia and low ammonemia is the most common presentation of these disorders. In 3-OAT deficiency, a potentially fatal disorder, there is a permanent ketosis with the only excretion of 3-hydroxybutyrate, acetoacetate and 3-hydroxyisovalerate. AAT patients usually excrete, in addition to the usual ketone bodies, 2-methyl-3-hydroxybutyrate and tiglylglycine; 2-methyl-acetoacetate may also be present. Both conditions can be identified by enzymatic analysis in cultured fibroblast. These disorders can mimic diabetic ketoacidosis or salicylism and can easily be missed. The knowledge of these ketolytic defects must severely question the complacent diagnosis of 'fasting ketoacidosis' or 'idiopathic ketotic hypoglycemia', mainly when severe metabolic acidosis is present.

Acetoacetates↗
PubMed1984

Stable isotope dilution analysis of orotic acid and uracil in amniotic fluid.

Rapid, sensitive and accurate stable isotope dilution assays were developed for the measurement of orotic acid and uracil in amniotic fluid. The method utilizes [15N2]orotic acid and [15N2]uracil as internal standards, isolation by liquid partition chromatography and quantitation by chemical ionization selected ion monitoring gas chromatography-mass spectrometry. Orotic acid at a concentration of 0.26 +/- 0.05 mumol/l and uracil at a concentration of 0.55 +/- 0.13 mumol/l were detectable in normal amniotic fluid. As affected fetuses with argininosuccinate synthetase or ornithine carbamoyl transferase deficiency showed no significant elevation of orotic acid and/or uracil in their surrounding amniotic fluids, this method unfortunately seemed not to be useful for prenatal diagnosis of these inherited disorders. Nevertheless, it provides significant advantage over available methods for the quantitation of orotic acid and uracil in which the analysis of these compounds must be very accurate, highly specific and sensitive (e.g. detection of heterozygosity for ornithine carbamoyl transferase deficiency).

Amniotic Fluid↗
PubMed1984

Hydroxy acid metabolites of branched-chain amino acids in amniotic fluid.

A method is described in which ammonia chemical ionization gas chromatography-mass spectrometry was utilized in the selected ion monitoring mode to provide an accurate, selective approach to the quantification in amniotic fluid of a number of hydroxylated organic acids derived from the metabolism of the branched-chain amino acids. 2-Hydroxy-n-caproic acid was employed as an internal standard and the hydroxy acids were isolated from amniotic fluid by liquid partition chromatography and the trimethylsilyl derivatives were quantified. Normal values have been obtained for 2-hydroxyisovaleric acid, the sum of 2-hydroxyisocaproic acid and 2-hydroxy-3-methylvaleric acid, 2-methyl-3-hydroxybutyric acid, 3-hydroxyisovaleric acid and 2-ethyl-3-hydroxypropionic acid. The method also provides data on the concentration of methylmalonic acid. The concentration of 2-hydroxyisovaleric acid was not useful in the prenatal diagnosis of a fetus with maple syrup urine disease. Elevated concentrations of 2-methyl-3-hydroxybutyric acid as well as methylmalonic acid were found in the amniotic fluid of two fetuses with methylmalonic acidemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1984

Prenatal diagnosis of glutaric aciduria type II by direct chemical analysis of dicarboxylic acids in amniotic fluid.

A method for the measurement of dicarboxylic acids in amniotic fluid was developed that utilizes isolation of the acids by liquid partition chromatography and quantification by ammonia chemical ionization selected ion monitoring, gas chromatography-mass spectrometry. The concentrations of dicarboxylic acids in ten normal samples of amniotic fluid (mumol/l +/- 1 S.D.) were glutaric acid 0.91 +/- 0.15, adipic acid 0.33 +/- 0.08, suberic acid 0.27 +/- 0.08, and sebacic acid 0.21 +/- 0.10. A highly elevated concentration of 14.48 mumol/l glutaric acid was found in the amniotic fluid of a pregnancy in which the fetus was affected with glutaric aciduria type II. Adipic, suberic and sebacic acids were also significantly elevated. The dicarboxylic acids were normal in the amniotic fluid of a pregnancy at risk for glutaric aciduria type II in which the fetus was unaffected. This method is suitable for the rapid prenatal diagnosis of glutaric aciduria types I and II and of potential value for the prenatal diagnosis of other inherited disorders in which dicarboxylic acids accumulate.

Adipates↗
PubMed1984

Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: contribution to the prenatal diagnosis of inherited disorders of leucine catabolism.

A quantitative assay for 3-hydroxyisovaleric acid in amniotic fluid was developed using D6-3-hydroxyisovaleric acid as an internal standard. 3-Hydroxyisovaleric acid was isolated by liquid partition chromatography and the amount determined by selected ion monitoring, ammonia chemical ionization gas chromatography-mass spectrometry of the trimethylsilyl derivatives. The concentration of 3-hydroxyisovaleric acid in ten normal amniotic fluid was 4.52 +/- 1.73 mumol/l. The level was elevated eight-fold in the amniotic fluid from a pregnancy resulting in the birth of a child with biotin-responsive multiple carboxylase deficiency. The stable isotope dilution assay of 3-hydroxyisovaleric acid in amniotic fluid is a rapid, sensitive and accurate method for the prenatal diagnosis of this disorder, and may be of value in the prenatal diagnosis of other inherited disorders of leucine catabolism.

Amino Acid Metabolism, Inborn Errors↗