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P Divry

Publications and source records attributed to P Divry.

At least 37 records · Page 2Linked to original sources
PubMed1996

Stable-isotope selected-ion monitoring quantification of methylmalonic acid in dried filter-paper urine samples.

Urea and creatinine were measured by Kodak Ektachem methods and methylmalonic acid by stable-isotope gas chromatography-mass spectrometry in 24 urine samples from patients with methylmalonic acidaemia. For each sample analyses were performed both directly on the liquid urine and on an aliquot which had been blotted onto filter paper and dried. There was good correlation between the methylmalonate/creatinine ratios in liquid and dried urine (r2 = 0.983). Urine dried on filter paper can be used advantageously for monitoring treatment in patients with this disorder.

Deuterium↗
PubMed1996

Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) is one of four straight-chain acyl-CoA dehydrogenase (ACD) enzymes, which are all nuclear encoded mitochondrial flavoproteins catalyzing the initial step in fatty acid beta-oxidation. We have used the very fast, Rapid Amplification of cDNA Ends (RACE) based strategy to obtain the sequence of cDNAs encoding human VLCAD from placenta and fibroblasts. Alignment of the predicted amino acid sequence of human VLCAD with those of the other human ACD enzymes revealed extensive sequence homology. Moreover, human VLCAD and human acyl-CoA oxidase showed extensive sequence homology corroborating the notion that these genes are evolutionarily related. Southern blot analysis of genomic DNA from hybrid cell lines was used to localize the VLCAD gene to human chromosome 17p11.2-p11.13105. Using Northern and Western blot analysis to investigate the tissue specific distribution of VLCAD mRNA and protein in several human tissues we showed that VLCAD is most abundant in heart and skeletal muscle. This agrees well with the fact that cardiac and muscle symptoms are characteristic for patients with VLCAD deficiency. Northern blot analysis and sequencing of cloned PCR amplified VLCAD cDNA from four unrelated patients with VLCAD deficiency showed that VLCAD mRNA was undetectable in one patient and that the other three have mutations in both VLCAD alleles. Western blot analysis of patient fibroblasts showed that the identified mutations result in severely reduced amounts of VLCAD protein. None of the patients harbored identical mutations suggesting that the mutational heterogeneity in VLCAD deficiency is large.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1994

Stroke, hemiparesis and deficient mitochondrial beta-oxidation.

We describe on a 3-year-old child referred for evaluation and therapy of a cerebral vascular accident with residual hemiplegia and partial epilepsy. Metabolic investigations initially showed normal urinary organic acids as well as normal blood and urinary amino acids. Blood carnitine fractions had been pathological and a secondary carnitine deficiency was diagnosed and treated by oral L-carnitine supplementation. During carnitine treatment, abnormal urinary acylcarnitine profiles were noticed with excessive amounts of several carnitine esters including propionylcarnitine, butyryl- and/or isobutyryl-carnitine, isovaleryl- and/or 2-methylbutyryl-carnitine, hexanoylcarnitine and octanoylcarnitine. Subsequently, an urinary organic acid profile suggestive of glutaric aciduria type II was recorded during a clinical decompensation crisis. Morphological and biochemical studies on skeletal muscle and skin fibroblasts were performed and confirmed the existence of a defect of the mitochondrial beta-oxidation pathways with lipidic myopathy, reduced palmitate and octanoate oxidation rates in cultured fibroblasts. Glutaric aciduria type II increases the list of metabolic disorders characterized by hemiplegia and other sequelae of brain ischaemia such as stroke-like episode, seizures, aphasia, ataxia and myoclonia, similar to those seen in MELAS.

Carnitine↗
PubMed1994

[Molecular pathology of type 1 primary hyperoxaluria].

Type 1 is the most common form of primary hyperoxaluria, also called oxalosis when systemic involvement has occurred. This recessive autosomal inherited inborn error of metabolism is characterized by a defect of alanine: glyoxylate aminotransferase (AGT), which is a specific liver enzyme. This protein is responsible for glyoxylate detoxification only when it is located in the peroxisome. The clinical and biochemical phenotypes are neither correlated with the residual catalytic activity of AGT nor with its immunoreactivity. Most patients display less than 2% catalytic activity (enz-) or no immunoreactive protein (crm-); peroxisome-to-mitochondrion mistargeting is the main feature of patients crm+/enz+ or crm+/enz-. The cDNA and genomic DNA have been cloned and sequenced and the gene has been located on the long arm of chromosome 2 in the q36-37 region. Three polymorphisms have been identified which are preferentially associated, leading to two alleles; six point mutations have been currently reported.

Alanine Transaminase↗
PubMed1993

3-Methylglutaconic aciduria in "optic atrophy plus".

Behr's syndrome consists of recessively inherited infantile optic atrophy, together with chronic neurological disturbances such as ataxia, extrapyramidal dysfunction, and juvenile spastic paresis. This syndrome was found to be relatively common among Iraqi Jews. For our study, 18 such patients underwent metabolic study. All 18 showed abnormally elevated excretion of 3-methylglutaconic acid in their urine. The basic enzymatic defect is as yet unknown. We recommend that patients with early optic atrophy, and especially those with motor dysfunction, be examined for this organic aciduria.

Adolescent↗
PubMed1993

2-Ketoglutarate dehydrogenase deficiency, a rare cause of primary hyperlactataemia: report of a new case.

Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) deficiency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progressively severe encephalopathy with axial hypotonia, psychotic behaviour, pyramidal symptoms and failure to thrive. Both children exhibited permanent lactic acidosis with acute episodes during emotional stress and various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibroblasts, the L/P ratio was greatly increased in the boy. No respiratory chain complex deficiency could be demonstrated in cultured fibroblasts or in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ketoglutarate oxidation was low in the absence of ADP and did not increase after ADP addition. 2-KGD deficiency was demonstrated in fibroblasts from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, suggesting that the E2 component could be responsible for the defect.

Acidosis, Lactic↗
PubMed1993

Reliable prenatal diagnosis of Canavan disease (aspartoacylase deficiency): comparison of enzymatic and metabolite analysis.

Prenatal diagnosis has been undertaken in 17 pregnancies in 15 families at risk for aspartoacylase deficiency. Amniocentesis was at 14-18 weeks gestation followed by measurement of amniotic fluid N-acetyl-L-aspartate (NAA) levels in all pregnancies and amniocyte aspartoacylase activity in most pregnancies. In one case amniocentesis was performed at 11 weeks gestation in conjunction with chorionic villus sampling. At 14-18 weeks of gestation, control levels of NAA were 0.30-2.55 mumol/L. The fetus was predicted to be affected in 8 of the pregnancies, 4 of which were confirmed by enzyme analysis on fetal tissue and 2 by the clinical and metabolic expression of Canavan disease in a newborn. In two cases there was no fetal tissue available for enzyme confirmation. One of these had the highest amniotic fluid NAA level (8.68 mumol/L) and in the other pregnancy there were two amniocenteses, both with markedly elevated levels. Of 9 fetuses predicted to be normal, 8 newborns were clinically and biochemically normal. A single case with amniotic fluid NAA in the normal range (1.56 mumol/L, measured in one laboratory only) resulted in an aborted fetus in whom aspartoacylase was deficient in cultured skin fibroblasts. We propose that amniotic fluid NAA levels remain the best predictor of an affected fetus and recommend that the assay be performed in multiple laboratories.

Amniotic Fluid↗
PubMed1993

Carnitine palmitoyl transferase I deficiency presenting as a Reye-like syndrome without hypoglycaemia.

An apparently healthy girl aged 2 years 9 months developed a coma with hepatomegaly within 24 h after an influenza-like infection. Plasma glucose and urinary organic acid profile were normal but plasma and urinary carnitine concentrations were increased. Despite symptomatic therapy, she died 11 days later. Oxidation of [1-14C] palmitic acid in the patient's fibroblasts was severely decreased (13% of controls). Further investigations revealed a deficiency of carnitine palmitoyl transferase I (CPT I) in the patient's fibroblasts (15% of controls) whereas CPT II activity was normal. Only four patients with CPT I deficiency have been reported so far. The subtle clinical and biochemical presentation of this disorder, which may account for the small number of cases diagnosed, is discussed.

Carnitine↗
PubMed1993

[Multiple acyl-CoA dehydrogenase deficiency. Report of 2 siblings].

The authors report on two siblings with a multiple acyl-CoA dehydrogenase deficiency. The first child died from a Reye's syndrome when he was 9 month-old. The diagnosis was made in the neonatal period in his brother. Early treatment with glucose and carnitine should prevent acute attacks.

Acyl-CoA Dehydrogenases↗