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Biomedical subjects

D Rabier

Publications and source records attributed to D Rabier.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Diagnosis of metabolic coma in children].

This article describes the metabolic investigations to be applied in any clinical situation consistent with a late acute form of inborn error of metabolism: unexplained coma with or without focal neurological manifestations, recurrent vomiting with lethargy, episodes of ataxia with or without behaviour disorder, fits of psychiatric troubles. In each of these situations, careful medical history is of major importance searching for previous clinical manifestations such as episodes of coma, ataxia or vomiting, anorexia, failure to thrive, developmental delay, all very suggestive of metabolic disorder. The association of neurological symptoms and abnormal hepatic tests is also of great value and must not lead to the diagnosis of Reye's syndrome without considering a metabolic defect of fatty acid oxidation, urea cycle, respiratory chain, or Wilson's disease. When looking for an etiological origin, it is mandatory to collect all the biological information at the same time, also knowing that metabolic abnormalities may be mild and transitory, and that many of them are non specific (metabolic acidosis, hyperlactacidemia, hyperammonemia, hepatic tests disturbances) being encountered in collapsus, shock and multiple organ failure syndrome.

Acute Disease↗
PubMed1994

[Protocol of metabolic investigations in hereditary metabolic diseases].

The authors describe a laboratory investigations protocol to be used by pediatricians facing conditions suggestive of inherited metabolic disorders. This protocol includes: 1) an emergency screening to be systematically performed during the acute clinical phase; 2) samplings to be kept frozen for possible secondary specific investigations according to the results of the emergency screening. In addition a perimortem protocol is also presented, to be applied in every lethal situations in which an inherited metabolic disorder is suspected. The equipment required in order for the clinician to properly perform the different investigations is also described.

Clinical Laboratory Techniques↗
PubMed1993

Prenatal diagnosis of ornithine transcarbamylase deficiency: results in Spfash mice.

Ornithine transcarbamylase (OTC) deficiency is a human X-chromosome-linked disease (McKusick 31125). The presence of OTC activity in the human placenta encouraged us to examine the possible diagnosis of the disease in an animal model (Spfash mice) by enzymatic assay on placental samples. A significant positive correlation (p < 0.02) was found between placental and hepatic activities; the pH dependence of OTC was similar in the placenta and liver when compared within normal or homozygous mutant mice. The apparent Km (ornithine) and Km (carbamoylphosphate) values of the enzyme did not show any significant differences when compared in both placentae and livers of normal fetuses. The use of OTC assay in the placenta for prenatal diagnosis of OTC deficiency in mouse fetuses obtained by the crossbreeding of Spfash/+ with +/Y has shown that our method has good diagnostic value. We made the diagnosis of OTC deficiency in male fetuses with a sensitivity and a specificity of 1.0. The + gene from the father in Spfash/+ animals is preferentially inactivated in extraembryonic tissues, explaining why very low placental OTC activity was observed in 12 of the 18 female fetuses studied. Because these 12 females have variable OTC activity in their livers, it is not possible to appreciate the true residual activity in their livers by measuring this activity in the placenta.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Intra- and interlaboratory quality control for assay of amino acids in biological fluids: 14 years of the French experience.

The functioning of an external quality-control scheme for amino acids set up in 1978 is described. Two measurements were made each month by participating laboratories on a control plasma sample provided by the quality-control center; freeze-dried samples were used from 1978 to 1989 and liquid samples since 1990. In addition, two "blind" samples were sent to the laboratories each year. Every 3 months, the overall results and those of the individual laboratories were analyzed statistically. The validity of the liquid sample control is demonstrated. The progressive improvement of results is commendable. In 1990, the coefficients of variation for all participants ranged from 8.4% for alanine to 23.5% for methionine. The standards used for calibration could contribute to the broad range of results, especially those for histidine and ornithine. The use of blind samples made it possible to detect problems of calibration, of linearity of measurement, of contamination, and of identification of unusual amino acids.

Amino Acids↗
PubMed1992

Human trifunctional protein deficiency: a new disorder of mitochondrial fatty acid beta-oxidation.

In this paper we report the identification of a new disorder of mitochondrial fatty acid beta-oxidation in a patient which presented with clear manifestations of a mitochondrial beta-oxidation disorder. Subsequent studies in fibroblasts revealed an impairment in palmitate beta-oxidation and in addition, a combined deficiency of long-chain enoyl-CoA hydratase, long-chain 3-hydroxyacyl-CoA-dehydrogenase and long-chain 3-oxoacyl-CoA thiolase. The recent identification of a multifunctional, membrane-bound beta-oxidation enzyme protein catalyzing all these three enzyme activities (Carpenter et al. (1992) Biochem. Biophys. Res. Commun. 183, 443-448; Uchida et al. (1992) J. Biol. Chem. 267, 1034-1041) suggested an underlying basis for this peculiar combination of three enzyme deficiencies. We show by means of size-exclusion chromatography that there is, indeed, a deficiency of the multifunctional beta-oxidation enzyme protein in this patient.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1992

Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.

We report an inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase deficiency, in three siblings with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth. Neurologic deterioration resulted in death at about 30 months of age. We propose low molar ratios of ketone bodies in plasma of neonates with congenital lactic acidosis as an indication of dysfunction of the tricarboxylic acid cycle.

Acidosis, Lactic↗
PubMed1992

Site specific screening for point mutations in ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is a frequent X linked disorder of the urea cycle which is responsible for lethal neonatal hyperammonaemia in males and for various clinical symptoms in heterozygous females. In order to improve the efficiency of our screening for mutant genotypes, we focused on molecular domains of functional or structural importance in the OTC gene, namely the carbamyl phosphate binding domain (encoded by the third exon) and the MspI restriction sites (CCGG) of the coding sequence (located in exons 2 and 7 respectively), as they contain mutation hot spots (CpG doublets). Using this procedure, we were able to identify three new mutant genotypes in OTC deficient children including one nonsense mutation (E 87 K, G 50 ter, G 162 R). Since genetic counselling for OTC deficiency is frequently difficult, molecular screening directed towards specific sites of the coding sequence could allow rapid detection of mutant genotypes and help solve diagnostic problems, especially when carrier status cannot be clarified easily.

Amino Acid Metabolism, Inborn Errors↗