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Biomedical subjects

C Charpentier

Publications and source records attributed to C Charpentier.

At least 109 records · Page 6Linked to original sources
PubMed1982

Congenital lactic acidosis, alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency.

A 6-month-old girl with vomiting, hypotonia and motor retardation was found to have elevated blood lactate, pyruvate, and branched chain amino acids associated with ketoglutaric aciduria. The combination of a congenital lactic acidosis with a variant form of maple syrup urine disease and ketoglutaric aciduria suggested a defect of a single component, common to pyruvate dehydrogenase, to branched chain ketoacid dehydrogenase, and to alpha-ketoglutarate dehydrogenase. Dihydrolipoyl dehydrogenase is the common component (E3). The three enzyme activities and the E3 component activity were found to be reduced in liver and cultured fibroblasts, thus confirming that a single defect of this component can result in a multiple deficiency involving several oxidative decarboxylation reactions.

Acidosis↗
PubMed1982

[Changes of plasma amino acids in cirrhotics treated with ornithine salts].

The plasma amino acid pattern of cirrhotic patients was determined before and after 24 h of continuous infusions of glucose, ornithine alpha-ketoglutarate (O alpha KG), ornithine chlorhydrate (ORN HCl) and sodium ketoglutarate (alpha CGNa). Before treatment, leucine, isoleucine, valine and glutamine levels were low. Tyrosine and methionine levels were high. (See formula in text) was low. Glucose infusions had no effect. O alpha KG increased levels of leucine, isoleucine, valine, alanine and arginine. Threonine, serine, glycine, aspartic acid, methionine, hemicystine, tyrosine and phenylalanine were significantly lowered. (See formula in text) increased. ORN HCl and alpha CGNa did not induce similar changes.

Amino Acids↗
PubMed1982

[Heterogeneity of leucinosis. Correlations between clinical manifestations, protein tolerance and enzyme deficiency].

Maple syrup urine disease (MSUD) is an inborn error of branched-chain aminoacid (BCAA) catabolism due to a defect of BC ketoacid decarboxylation. Beside the classical form of the disease, general variant forms have been recently reported. From our personal experience in 21 patients consisting of 14 patients with classical MSUD and 7 patients with "variant" forms (1 intermittent, 2 subacute forms, 1 lipoamide dehydrogenase deficiency and 3 composite heterozygotes), we tried to correlate clinical features with protein tolerance and enzyme activity. All classical forms share an acute neonatal presentation, with a low leucine tolerance (m +/- SD = 465 +/- 88 mg per day), and a very low enzyme activity (m +/- SD = 2.5 +/- 1.5% of controls), mild variations being consistent with a possible polyallelism within this group. All "variant" forms share a late onset with a reasonable leucine tolerance (2-3 grams per day) and a fair enzyme activity, ranging from 7 to 20% of controls. However, no strict correlation could be found between the severity of the outcome and the extent of the residual enzyme activity, since acute episodes or chronic deterioration occurred even in "variants", irrespective of the level of their enzyme activity. Finally, our data suggest that variant forms could result from a composite heterozygotism, combining heterozygotism for the gene of classical MSUD and heterozygotism for a "petite" mutation, undetectable when isolated. The occurrence of classical MSUD and "variant" forms of the disease within a single family of our series further supports this hypothesis.

Adolescent↗
PubMed1982

[Double deficiency of sulfite and xanthine oxidase causing encephalopathy and due to a hereditary anomaly in the metabolism of molybdenum].

The clinical features and biological results in a second patient with a metabolic defect of the molybdenum cofactor are described. The first case was reported in 1978 by Duran et al. Their clinical description was similar with early encephalopathy and myoclonial and dislocation of the lens. Biologically, this condition is characterised by secondary hypo-uricemia and hypo-uricuria due to xanthine oxidase deficiency and by sulphituria, resulting from sulphite oxidase deficiency. These two enzymes have a common hepatic molybdenum cofactor, the structure and metabolism of which are only partially known.

Brain Diseases, Metabolic↗
PubMed1982

[Prolidase and manganese deficiency. Apropos of a case: diagnosis and treatment].

Prolidase deficiency, transmitted on an autosomic recessive mode upsets skin healing and facilitates the occurrence of chronic cutaneous ulcerations. A 36-year-old woman has been followed since the age of 12 for ulcerations and erythematous erysipelatoid plaques of the lower limbs. Two episodes of agranulocytosis were induced by intake of sulfonamides at the age of 17. The same accident had been observed in her aunt. As the aetiological research of ulcers was negative, a prolidase deficit was suspected. The diagnosis is ascertained by the existence of an immunopeptiduria of 5 mmol/24 hours (normally absent). The predominating dipeptides are glycilproline and phenylalanine proline. R-hydroxyproline dipeptide were present at a lesser degree. Urinary hydrolysis showed elevation of free proline (x 10) and hydroxyproline (x 6). Dosage of erythrocytes prolidase evidenced an activity 2 p. 100 of the normal in one case and 55 p. 100 and 49 p. 100 in the parents. Treatment by cofactors of prolidase (vitamine C and manganese) reduced immunopeptiduria, suppressed inflammatory outbreaks and allowed a transient cicatrisation. This tenth case of prolidase deficiency underlines the character of the disease: recurrent ulcers (7/10), erysipelatoid plaques (3/10), ecchymosis (4/10), telangiectatic scars (7/10), edema (1/10), early canitias (1/10). Partial correction by cofactors evokes a prolidase deficiency by inactivation of the enzymes activating systems.

Adult↗
PubMed1981

Neonatal glutaric aciduria type II: an X-linked recessive inherited disorder.

A new case of neonatal glutaric aciduria type II is reported. Neonatal acidosis, hypoglycemia, and hyperammonemia were characteristic. The baby died at four days of age. Organic acid analysis revealed massive glutaric aciduria with elevated concentrations of butyric, isobutyric, n-butyric, and isovaleric acid in his urine. The baby's pedigree suggested strongly an X-linked recessive mode of inheritance. Clinically, biochemically, and genetically glutaric aciduria type II is an heterogeneous disorder. The neonatal form is an X-linked inherited disorder which presents early in life, and is associated with metabolic acidosis, hypoglycemia, and hyperammonemia, and leads to death in the neonatal period. The mild form is an autosomal recessive inherited disease which may present even in adults, and is associated with recurrent hypoglycemia without ketosis and usually improves. Nevertheless the same unusual organic acid pattern is observed in both forms. The basic biochemical defect must be distinct and has not been elucidated.

Acidosis↗
PubMed1981

Biotin dependent multiple carboxylase deficiency presenting as a congenital lactic acidosis.

Two patients presented in early childhood with (i) alopecia, skin rashs, and dermatitis, (ii) severe hypotonia, ataxia and motor retardation, (iii) frequent episodes of ketoacidosis with hyperlactacidemia. Propionic and methylcrotonic aciduria only appeared on high protein diet. Mitochondrial biotin-dependent carboxylase activities were decreased in the liver and leukocytes, but were similar to control values in fibroblasts cultured in a biotin-free medium. In addition, the plasma biotin was found to be significantly lower than in control subjects. These disorders responded to biotin administration, pointing to biotin-dependent multiple carboxylase deficiencies (MCD). Our report stresses the polymorphism of MCD and suggests that MCD could be of two types: impaired vitamin metabolism (absorption, plasma transport), might result in low plasma biotin with generalized MCD involving acetyl CoA carboxylase. Defective mitochondrial holocarboxylase synthetase might lead to a pure mitochondrial MCD, with fibroblastic deficiency and presumably normal biotin metabolism.

Acidosis↗
PubMed1981

Brain uptake of 11C-methionine in phenylketonuria.

The brain uptake of 11C-methionine was studied in 26 children with classical phenylketonuria; one adult was used as a control. Labelled methionine uptake in brain was first measured during a low phenylalanine diet and again one week later after a load of phenylalanine. Ten children aged 1 to 30 months were studied twice at intervals of several months. In children having a phenylalaninemia less than or equal to 0.3 mumoles . ml-1, a decrease in methionine brain uptake was observed with increasing age, with the largest change occurring during the first year of life. After the phenylalanine load, a mean increase in phenylalaninemia by a factor of ten was accompanied by a mean decrease in brain methionine uptake by a factor of two while blood methionine remained unchanged. Brain activity curves increased with time for children younger than one year and having phenylalaninemia less than 0.6 mumoles . ml-1. After the age of 2 most patients had a decreasing curve regardless of the blood phenylalanine level. This study indicates that 11C-methionine brain uptake may be taken as an index of blood barrier permeability to essential amino acids, and of brain maturation. The results obtained suggest that an increase in phenylalaninemia to levels greater than 0.6 mumole . ml-1 induces a modification in brain uptake of amino acids, primarily during the first two years of life.

Adult↗
PubMed1981

Metabolic abnormalities observed in the rat after administration of sodium dipropylacetate.

Sodium dipropylacetate (DPA) was administered to 10 normally fed rats and 5 biotin-deficient rats. The effects of DPA were measured on propionic acid and glycine levels in urine and blood; and on hepatic propionyl-CoA carboxylase (PCC) activity. No abnormal amounts of propionic acid were found in the blood and urine of the treated rats. Hyperglycinemia and significant constant hyperglycinuria were observed in all animals given DPA, but without significant differences between normal and biotin-deprived rats. DPA treatment did not affect PCC activity in vivo or vitro. These results indicate that the abnormalities of the glycine metabolism are not linked to an accumulation of propionic acid due to PCC inhibition by DPA.

Animals↗
PubMed1981

Variation in plasma ketone bodies during a 24-hour fast in normal and in hypoglycemic children: relationship to age.

The variations in blood ketone bodies, blood glucose, and insulin were studied in 19 normal and 14 hypoglycemic children, 4 months to 13 years of age, during a 24-hour fast. Except in four patients (two with hyperinsulinism and two with congenital defect in ketogenesis), a significant increase in blood ketone bodies was observed in both controls and patients. A progressive decrease in glucose concentrations was observed up to but not after 20 hours. A highly negative correlation between blood ketone bodies and blood glucose was found, with a large dispersion of blood ketone bodies, especially for those corresponding to the blood glucose between 45 and 65 mg/dl. This dispersion was consistently reduced in a homogenous age group of 4 to 6 years with similar glucose values. There was a positive correlation between age and blood glucose from hour 21 on, and an inverse relationship between age and blood ketone bodies from hour 15 on. The same high inverse relationship between age and blood ketone bodies was again observed when the variable of glucose concentration was factored out, demonstrating that the variation in blood ketone bodies is indeed related to age. These findings need to be taken into account in the interpretation of fasting blood ketone bodies, especially when used as an aid in the diagnosis of the various forms of childhood hypoglycemia, and of hypoketotic states.

Age Factors↗
PubMed1981

[Multiple biotin-dependent carboxylase deficiencies (author's transl)].

Two patients presented in early childhood with: 1) alopecia, skin rashs, and candida dermatitis; 2) severe hypotonia, ataxia and motor retardation; 3) frequent episodes of ketoacidosis with hyperlactacidemia. Propionic and methylcrotonic aciduria only appeared on hyperprotidic diet. Mitochondrial biotin-dependent carboxylase activities were decreased in the liver and leukocytes, but were paradoxically normal in cultured fibroblasts whatever the biotin content of the medium. These disorders responded to biotin administration, pointing to multiple biotin-dependent carboxylase deficiencies (MCD). Our report stresses the polymorphism of MCD: major discrepancies concern predominance of carboxylase deficiency, expression of MCD in cultured fibroblasts, and possible involvement of a cytoplasmic biotin enzyme, acetyl CoA carboxylase (ACC). Finally, we suggest that MCD could be of two types: impaired biotin metabolism (absorption, transport, activation) might result in generalization MCD involving ACC. Defective holocarboxylase synthetase might lead to a pure mitochondrial MCD with fibroblastic deficiency and presumably skin integrity.

Acetyl-CoA Carboxylase↗