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1.
Mol Genet Metab Rep ; 2: 25-31, 2015 Mar.
Article in English | MEDLINE | ID: mdl-28649521

ABSTRACT

Pyruvate carboxylase (PC) is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA) cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A). Diagnosis was nearly fortuitous, resulting from the revision of an initial diagnosis of mitochondrial complex IV (C IV) defect. The patient presented with severe lactic acidosis and pronounced ketonuria, associated with lethargy at age 23 months. Intellectual disability was noted at this time. Amino acids in plasma and organic acids in urine did not show patterns of interest for the diagnostic work-up. In skin fibroblasts PC showed no detectable activity whereas biotinidase activity was normal. We had previously reported another patient with the severe form of PC deficiency and we show that she also had secondary C IV deficiency in fibroblasts. Different anaplerotic treatments in vivo and in vitro were tested using fibroblasts of both patients with 2 different types of PC deficiency, type A (patient 1) and type B (patient 2). Neither clinical nor biological effects in vivo and in vitro were observed using citrate, aspartate, oxoglutarate and bezafibrate. In conclusion, this case report suggests that the moderate form of PC deficiency may be underdiagnosed and illustrates the challenges raised by energetic disorders in terms of diagnostic work-up and therapeutical strategy even in a moderate form.

2.
Arch Pediatr ; 19(9): 959-69, 2012 Sep.
Article in French | MEDLINE | ID: mdl-22884749

ABSTRACT

Inherited metabolic diseases are mostly due to enzyme deficiency in one of numerous metabolic pathways, leading to absence of a compound downstream from and the accumulation of a compound upstream from the deficient metabolite(s). Diseases of intoxication by proteins (aminoacidopathies, organic acidurias, urea cycle defects) and by sugars (galactosemia, fructosemia) usually do not give prenatal symptoms since mothers protect their fetuses from pathological metabolite accumulation. A well-known exception is hypoplasia of corpus callosum, as is sometimes observed in nonketotic hyperglycinemia and sulfite oxidase deficiency. Conversely, women with phenylketonuria "poison" their fetus if they are not treated (spontaneous abortions, intrauterine growth restriction [IUGR], cardiac malformations, and brain disease). Amino acid synthesis defects can lead to prenatal symptoms: microcephaly in serine deficiency (detectable by amino acid analysis in fetal cord blood), and brain malformations in glutamine synthetase deficiency. Impaired folate metabolism is involved in a large fraction of neurodevelopmental defects referred to as spina bifida, yet the underlying genetic component(s) are largely unknown. Energy metabolism diseases caused by defects in the synthesis or utilization of relevant metabolites lead to organ dysfunctions or malformations, but prenatal diagnosis is usually impossible unless genetic analysis can rely on a previously affected child in the family. A somewhat intermediate condition is defects of mitochondrial beta-oxidation of fatty acids, as they may sometimes be symptomatic prenatally (notably the HELLP syndrome or other presentations), and in this case, organic acid and acylcarnitine analysis in amniotic fluid can be informative in the absence of an index case. In contrast, complex molecule diseases commonly give prenatal symptoms that may permit the diagnosis even in the absence of index cases: hydrops fetalis and skeletal anomalies in lysosomal storage diseases, hydrops fetalis in congenital disorders of glycosylation (CDG) and transaldolase deficiency, brain malformations in O-glycosylation defects, brain malformations, kidney cysts and skeletal anomalies in peroxysomal diseases (Zellweger syndrome), syndactyly, genitalia malformations, and IUGR in Smith-Lemli-Opitz (SLO) syndrome. Although many metabolic disorders show biochemical abnormalities during fetal development that are informative for prenatal diagnosis, only a fraction of them are clinically/sonographically symptomatic before birth, thus allowing for prenatal diagnosis in the absence of an index case, i.e., serine deficiency, some fatty acid beta-oxidation defects, transaldolase deficiency, lysosomal diseases, CDG, Zellweger syndrome, and SLO syndrome.


Subject(s)
Fetal Diseases/diagnosis , Metabolism, Inborn Errors/diagnosis , Prenatal Diagnosis , Energy Metabolism , Female , Humans , Macromolecular Substances/metabolism , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications
3.
Prenat Diagn ; 30(1): 43-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19950217

ABSTRACT

BACKGROUND: Normative data for amniotic fluid (AF) levels of organic acids at different gestational ages are lacking. They can provide a useful framework to investigate the accuracy of prenatal diagnosis for organic acidemias. METHODS: We report on the concentration of 21 organic acids in AF obtained by gas chromatography/mass spectrometry between the 12th and 34th weeks of gestation from 92 pregnancies that were not at risk for organic acidurias. RESULTS: We infer normal reference values that can be compared with 134 pregnancies at risk for several metabolic conditions, that is, propionic acidemia, methylmalonic acidemia (methylmalonyl-CoA mutase deficiency or defects in cobalamin metabolism), 4-hydroxybutyric acidemia, glutaric acidemia and pyroglutamic acidemia. CONCLUSION: Most of the metabolites tested did not show conspicuous variations across gestational ages in normal fetuses, with ranges that were consistently similar to available reference values from pooled samples in previous reports. With rare exceptions, knowledge of pathological versus normal values for relevant metabolites leads to clear-cut differentiation of affected versus unaffected fetuses. Nevertheless, it is strongly recommended that mutational analysis and/or additional biochemical approaches complement organic acid analysis for an adequate diagnostic workup.


Subject(s)
Amino Acid Metabolism, Inborn Errors/diagnosis , Amniotic Fluid/chemistry , Carboxylic Acids/analysis , Prenatal Diagnosis/methods , Adult , Female , Gestational Age , Humans , Pregnancy , Prenatal Diagnosis/statistics & numerical data , Reference Values
4.
Clin Biochem ; 40(9-10): 692-8, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17459360

ABSTRACT

BACKGROUND: Cystinosis is a rare autosomal recessive disorder characterized by an accumulation of intralysosomal cystine due to a defect in cystine transport across the lysosomal membrane. This disorder can be treated specifically using high doses of cysteamine. Accurate measurement of intracellular cystine content is necessary for the diagnosis and monitoring of treatment with cysteamine. Here we describe a new method to measure intracellular cystine. It relies on a liquid chromatography-tandem mass spectrometry assay. We compare this novel method with the cystine-binding protein assay. METHOD: Cells were isolated and lysed in the presence of N-ethylmaleimide to avoid interference from cysteine. After deproteinization, addition of stable isotope d6 cystine and butylation, cystine was measured using an API 3000 MSMS. RESULTS: The cystine assay was linear to at least 50 micromol/L. Within-run and between-run coefficients of variation were 2.9% and 5.7% respectively. CONCLUSION: It is possible to measure very low concentrations of intracellular cystine with liquid chromatography-tandem mass spectrometry. The results obtained with this novel method correlate very well with those obtained using the cystine-binding protein assay.


Subject(s)
Chromatography, Liquid/methods , Cystine/analysis , Granulocytes/chemistry , Tandem Mass Spectrometry/methods , Cystinosis/diagnosis , Escherichia coli Proteins/metabolism , Humans
5.
Prenat Diagn ; 26(9): 814-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16821251

ABSTRACT

BACKGROUND: In the present study, we report the results of 132 prenatal diagnoses performed on chorionic villi and cell-free amniotic fluid obtained simultaneously at 12-13 weeks of gestation. In addition, we report the result of 59 prenatal diagnoses performed at 12-13th week using amniotic fluid only. METHODS AND RESULTS: A total of one fetal loss (1/191) was observed when a sample of amniotic fluid was obtained at around 12-13 weeks, whereas three losses (3/82) were observed after midtrimester amniocentesis. We attribute this finding to the fact that only a very small volume of amniotic fluid was sampled using a very small needle. CONCLUSION: From these data it appears that when a couple is facing a high risk of recurrence of some metabolic diseases, the study of chorionic villus and amniotic fluid sampled simultaneously offers a safe and reliable method of early prenatal diagnosis.


Subject(s)
Amniocentesis , Chorionic Villi Sampling , Metabolism, Inborn Errors/diagnosis , Prenatal Diagnosis , Abortion, Spontaneous/etiology , Amniocentesis/adverse effects , Female , Humans , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, First
6.
Arch Mal Coeur Vaiss ; 98(2): 145-52, 2005 Feb.
Article in French | MEDLINE | ID: mdl-15787307

ABSTRACT

Although there is a high degree of proof relating plasma homocysteine levels to cardiovascular risk, the role of homocysteine as a causal cardiovascular risk factor remains controversial. Prospective long-term clinical trials in high cardiovascular risk populations usually show a positive relationship between plasma homocysteine and the degree of cardiovascular risk. However, shorter term studies and/or those carried out in populations with lower cardiovascular risk show either a weaker correlation or no relationship at all. To date no study has shown proof of the reversibility of cardiovascular risk due to hyperhomocysteinaemia; nevertheless, a number of studies using intermediate criteria support the hypothesis of a benefit due to reduction of plasma homocysteine levels. A number of therapeutic trials published with clinical criteria have not shown convincing results in either direction. A number of interventional trials are underway: notably the SUFOLOM 3 trial in France, and the question of a benefit on cardiovascular risk by reducing homocysteine levels should be answered in the next few years. In the meantime, with the exception of homocysteinuria in which therapeutic strategies have shown their efficacy in the reduction of atherothrombotic risk with high levels of proof, the authors do not recommend the treatment of mild hyperhomocysteinaemia in any clinical setting other than "clinical trials" and certain "compassionate" indications such as early and/or recurrent vascular events associated with hyperhomocysteinaemia in the absence of conventional risk factors.


Subject(s)
Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Hyperhomocysteinemia/complications , Cardiovascular Diseases/blood , Clinical Trials as Topic , Folic Acid/therapeutic use , Hematinics/therapeutic use , Humans , Hyperhomocysteinemia/therapy , Risk Factors , Vitamin B Complex/therapeutic use
7.
Prenat Diagn ; 22(6): 456-8, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12116302

ABSTRACT

Prenatal diagnosis of citrullinemia is performed using a direct argininosuccinate synthetase (ASS) assay on chorionic villi (CV) and citrulline concentration measurement in early amniotic fluid (AF). Here we report the results of 40 prenatal diagnoses performed using this method, discuss the difficulties encountered in interpreting the results, and propose the use of the citrulline/ornithine+arginine ratio (which is more discriminatory than citrulline concentration alone) when performing prenatal diagnosis of citrullinemia.


Subject(s)
Amniocentesis , Amniotic Fluid/chemistry , Arginine/analysis , Citrulline/analysis , Citrullinemia/diagnosis , Ornithine/analysis , Argininosuccinate Synthase/analysis , Argininosuccinate Synthase/deficiency , Chorionic Villi Sampling , Female , Humans , Pregnancy , Sensitivity and Specificity
9.
Kidney Int ; 56(6): 2292-6, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10594808

ABSTRACT

UNLABELLED: Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. BACKGROUND: Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients. METHODS: In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin. RESULTS: Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time. CONCLUSIONS: Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.


Subject(s)
Hyperhomocysteinemia/drug therapy , Kidney Failure, Chronic/complications , Leucovorin/administration & dosage , Pyridoxine/administration & dosage , Renal Dialysis , Adult , Aged , Erythrocytes/chemistry , Female , Humans , Hyperhomocysteinemia/etiology , Injections, Intravenous , Kidney Failure, Chronic/therapy , Leucovorin/analysis , Leucovorin/blood , Male , Middle Aged , Tetrahydrofolates/administration & dosage , Vitamin B 12/blood
10.
J Inherit Metab Dis ; 21(8): 812-22, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9870206

ABSTRACT

Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disease remains a matter of debate. Testing for the 677C-T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients. Conversely, plasma homocysteine levels were substantially higher in patients than in controls. A slight interaction between the 677C-T MTHFR polymorphism and homocysteinaemia was observed in the patient group only, while a negative correlation between fasting homocysteine and plasma folate levels was found in all individuals homozygous for the 677C-T MTHFR genotype, irrespective of vascular disease. These data suggest that the 677C-T MTHFR polymorphism is not a major determinant of the vascular disease but contributes to increased plasma homocysteine concentration in conjunction with low plasma folate levels.


Subject(s)
Homocysteine/blood , Oxidoreductases/genetics , Polymorphism, Genetic , Vascular Diseases/genetics , 5,10-Methylenetetrahydrofolate Reductase (FADH2) , Adolescent , Adult , Aged , Aged, 80 and over , Erythrocytes/metabolism , Female , Folic Acid/blood , Genotype , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Middle Aged , Risk Factors , Vascular Diseases/blood , Vitamin B 12/blood
11.
J Inherit Metab Dis ; 21(8): 823-8, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9870207

ABSTRACT

We describe four new mutations in the cystathionine beta-synthase gene: three point mutations localized in exons 3, 9 and 10 and one mutation in exon 12 which results in stop codon.


Subject(s)
Cystathionine beta-Synthase/genetics , Homocystinuria/genetics , Mutation , Consanguinity , Exons , Homocystinuria/enzymology , Homozygote , Humans , Male , Mutation, Missense , Polymorphism, Single-Stranded Conformational
12.
Prenat Diagn ; 18(9): 947-52, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9793978

ABSTRACT

Prenatal diagnosis for combined methylmalonic aciduria and homocystinuria was performed in five at-risk pregnancies by determination of methylmalonic acid (MMA) and total homocysteine (Hcy) in amniotic fluid supernatant. The incorporation rate of [14C] propionate (+/- OHCbl) and the synthesis of cobalamin derivatives in cultured amniocytes were investigated as well as the [14C] MTHF incorporation rate in intact chorion biopsy. Our experience showed that total Hcy and MMA were clearly elevated in amniotic fluid of affected fetuses. Both the study of [14C] propionate incorporation and that of cobalamin synthesis in cultured amniocytes are useful to confirm the results of metabolite determination. The incorporation of [14C] MTHF in intact chorion biopsy seems not to be a reliable diagnostic method.


Subject(s)
Amino Acid Metabolism, Inborn Errors/diagnosis , Amniocentesis , Chorionic Villi Sampling , Homocystinuria/diagnosis , Methylmalonic Acid/urine , Amniotic Fluid/chemistry , Cells, Cultured , Chorion/metabolism , Cobamides/biosynthesis , Female , Gestational Age , Homocysteine/analysis , Humans , Male , Methylmalonic Acid/analysis , Pregnancy , Propionates/metabolism , Tetrahydrofolates/metabolism , Vitamin B 12/analogs & derivatives , Vitamin B 12/biosynthesis
13.
Nephrol Dial Transplant ; 13(7): 1792-8, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9681730

ABSTRACT

BACKGROUND: Cardiovascular accidents are the major cause of morbidity and mortality in renal transplant recipients. However, there is little information concerning carotid atherosclerotic wall changes in renal transplant recipients, their relationship with cardiovascular accidents and their possible association with cardiovascular risk factors in such patients. METHODS: Between April 1991 and December 1997, we prospectively assessed cardiovascular accidents in 79 renal transplant recipients who had received a transplant at our institution before January 1, 1986. Carotid morphology by B-mode ultrasonography, relevant clinical and laboratory cardiovascular risk factors, including lipid abnormalities and total homocyst(e)ine, were determined at the start of the follow-up period. Seventeen healthy subjects matched for age and sex with renal transplant recipients served as controls who volunteered for ultrasonographic examination of carotid arteries. RESULTS: Nine patients experienced cardiovascular events during the period of follow-up. Compared with healthy, age- and sex-matched control subjects (n = 17), the frequency of carotid plaques was higher in renal transplant recipients with cardiovascular events (n = 9), but not in those without such events (n = 70). The frequency of cardiovascular accidents was related to the number of carotid plaques (4, 17 and 24% for no plaque, one plaque and > 1 plaque respectively, P < 0.04). However, by multivariate analysis, serum total cholesterol [odds ratio (OR) of 1.8 for each 1.0 mM, P < 0.07) and the presence of diabetes mellitus (OR of 28.4 for presence, P < 0.01) were the only predictors of cardiovascular events in such patients, whereas the presence of carotid plaques was not. Moreover, neither serum lipoprotein (a) nor total homocyst(e)ine concentrations could be identified as risk factors. CONCLUSIONS: This prospective study shows that although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events. Consequently, the assessment of carotid atherosclerosis may not be clinically useful for the systematic identification of renal transplant recipients with an increased risk of developing cardiovascular events.


Subject(s)
Arteriosclerosis/etiology , Carotid Artery Diseases/etiology , Kidney Transplantation/adverse effects , Adult , Cardiovascular Diseases/etiology , Cholesterol/blood , Diabetes Complications , Female , Humans , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Risk Factors
14.
Int J Cardiol ; 60(3): 295-300, 1997 Aug 08.
Article in English | MEDLINE | ID: mdl-9261641

ABSTRACT

Homocysteine is a graded risk factor for the incidence of stroke and for the degree of carotid atherosclerosis. Homocysteine is also a graded risk factor for the incidence of myocardial infarction but we do not know its precise relations to the severity of atherosclerosis in coronary patients. Seventy five symptomatic coronary patients were recruited for the study. Fifty of these patients had coronary artery disease only and were compared in a case-control manner to 50 healthy controls matched for age and sex. The 25 other coronary patients had also symptoms in another atherosclerotic territory (cerebral, peripheral or both) and were also compared to 25 matched controls. Mean plasma homocysteine level was significantly higher in coronary patients than in controls (11.7 +/- 0.7 mumol l-1, n = 50 versus 9.9 +/- 0.5 mumol l-1, n = 50, p < 0.05). Homocysteine in patients with symptomatic atherosclerosis in two or three arterial sites was 15.7 +/- 1.5 mumol l-1 which differed significantly from matched controls and from patients with coronary artery disease only (p = 0.01). The extent of coronary atherosclerosis evaluated by an angiographic coronary score correlated weakly to plasma homocysteine levels (r = 0.25, p < 0.05). The patients with both hypertension and high levels of homocysteine (> 11.3 mumol l-1, median value) had more severe coronary atherosclerosis (coronary score of 16.3 +/- 2.3 versus 11.9 +/- 0.9, p < 0.05) and more diffuse atherosclerosis (number of atherosclerotic territories of 1.5 +/- 0.2 versus 1.2 +/- 0.7, p = 0.08) than the coronary patients without this association. There were no other high risk association when considering the other classical risk factors. Thus, the highest levels of homocysteine were present in patients with coronary disease and another symptomatic localisation of atherosclerosis. A small gradient in the extent of coronary atherosclerosis was found with increasing levels of homocysteine. The presence of both hypertension and hyperhomocysteinemia was associated with more severe coronary atherosclerosis.


Subject(s)
Coronary Artery Disease/blood , Homocysteine/blood , Biomarkers/blood , Case-Control Studies , Coronary Angiography , Coronary Artery Disease/etiology , Diabetes Complications , Diabetes Mellitus/blood , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Hypertension/blood , Hypertension/complications , Male , Middle Aged , Risk Factors , Smoking/adverse effects , Smoking/blood
16.
Arch Mal Coeur Vaiss ; 89(10): 1241-6, 1996 Oct.
Article in French | MEDLINE | ID: mdl-8952820

ABSTRACT

Homocystein is at the crossroads of the metabolic pathways of sulphuric amino acids. Homocystinuria is a congenital autosomal recessive disease, usually related to cystathionine beta-synthetase deficiency. Children with homozygotic forms of the disease have early vascular complications which represent the main cause of death. Moderately elevated serum homocystein levels are related to two major genetic factors (heterozygotic cystathionine beta-synthetase deficiency and mutation of the 5-10 methylene tetrahydrofolate reductase) and several minor, genetic and non-genetic factors (folic acid, vitamins B6 and B12 and betain deficiencies). Previous studies have suggested that hyperhomocysteinaemia could be a cardiovascular risk factor. This study was based on 222 subjects including 102 consecutive patients with angiographically documented coronary artery disease and 120 control subjects without vascular disease. No relationship was observed between serum homocystein concentrations and the classical cardiovascular risk factors. Coronary patients had higher average homocystein concentrations than control subjects (11.27 +/- 0.52 vs 8.77 +/- 0.31 mumol/l); p < 0.0001): moreover, the prevalence of hyperhomocysteinaemia (> 15.67 mumol/l) was higher in the coronary group (15.7%) than in the controls (2.5%). A significant relationship was also observed between homocystein concentrations and the severity of the coronary disease (defined by a coronary score) and the number of diseased vascular territories. These results underline the relationship between homocystein and vascular risk, especially that of coronary artery disease. The treatment of hyperhomocysteinaemia by folic acid supplements is effective in correcting plasma levels, without side effects and at a relatively low cost.


Subject(s)
Coronary Disease/blood , Homocysteine/blood , Adult , Aged , Aged, 80 and over , Case-Control Studies , Coronary Disease/epidemiology , Female , Folic Acid/therapeutic use , France/epidemiology , Hematinics/therapeutic use , Humans , Male , Middle Aged , Prevalence , Risk Factors , Severity of Illness Index
17.
Prenat Diagn ; 16(7): 623-8, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8843471

ABSTRACT

In this study we have measured the concentration of 24 amino acids and total homocysteine in amniotic fluids obtained between the tenth and 32nd week of gestation from pregnancies not at risk for metabolic diseases. These results are used as reference values to which are compared values obtained from pregnancies at risk for citrullinaemia, argininosuccinic aciduria, HHH (hyperornithinaemia, hyperammonaemia and homocitrullinaemia) syndrome, cobalamin metabolism disorders (CblC or CblD), and sulphite oxidase deficiency. We discuss the helpfulness of amino acid analysis in amniotic fluid for prenatal diagnosis of aminoacidopathies.


Subject(s)
Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acids, Sulfur/analysis , Amniotic Fluid/chemistry , Argininosuccinic Acid/analysis , Citrulline/analysis , Ornithine/analysis , Prenatal Diagnosis/methods , Amino Acids, Sulfur/metabolism , Argininosuccinic Acid/metabolism , Chromatography, Ion Exchange , Citrulline/metabolism , Female , Gestational Age , Humans , Ornithine/metabolism , Oxidoreductases Acting on Sulfur Group Donors/deficiency , Pregnancy , Reference Values , Vitamin B 12/metabolism
19.
Presse Med ; 25(11): 531-6, 1996 Mar 30.
Article in French | MEDLINE | ID: mdl-8731796

ABSTRACT

OBJECTIVES: The aim of this work is to study the signification of an extensive biological evaluation in patients with "unexplained" thrombosis. We studied 78 patients with more than one arterial and/or venous thromboembolic event. METHODS: Fifty-four patients were admitted for unexplained deep venous thrombosis (group I, n = 19, 9 men and 10 women) and/or arterial thrombosis (group II, n = 35, 21 men and 14 women). A third group (group III) included 24 patients (13 men, 11 women) known to have a pathologic state which can lead to a thrombotic event. RESULTS: The patients in both groups I and II had, more often than normal subjects, a high level of homocysteinemia (26% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 (18.5% vs 3%, p < 0.001) and antiphospholipid antibodies (13% vs 3%, p < 0.02). We also found a significant association between an increase of erythrocytic aggregation and arterial thrombosis (group II). In the third group, for both arterial (n = 14) and venous (n = 10) thrombosis, we found a high level of anticardiolipin antibodies (25% vs 3%, p < 0.001), anti-beta 2 glycoprotein 1 antibodies (12.5% vs 3%, p < 0.05) and abnormal erythrocytic aggregation (16.5% vs 3%, p < 0.01). In these 3 groups the other studied parameters (Lp(a), platelet aggregation, cryoglobulin, cryofibrinogen, antinuclear antibodies, anticytoplasm antibodies, plasma and urine immunoelectrophoresis, protein C, protein S, antithrombin III, plasminogen) were not different from levels observed in normal subjects. CONCLUSION: An extensive biological analysis, including plasma homocystein level, anticardiolipin antibodies, anti-beta 2 glycoprotein 1 antibodies and a study of the erythrocytic aggregation would appear to be of value in patients presenting recurrent arterial or venous thromboembolic events. Specific therapy can be applied in case of abnormal results continued anticoagulant therapy for anticardiolipin and anti-beta 2 glycoprotein 1 antibodies, and a vitamin therapy for increased homocysteinemia.


Subject(s)
Thrombosis/blood , Adolescent , Adult , Aged , Antibodies, Anticardiolipin/analysis , Antibodies, Antiphospholipid/analysis , Apolipoproteins , Erythrocyte Aggregation , Evaluation Studies as Topic , Female , Glycoproteins/immunology , Homocysteine/blood , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Thrombosis/etiology , Thrombosis/immunology , beta 2-Glycoprotein I
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