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D Rabier

Publications and source records attributed to D Rabier.

At least 19 recordsLinked to original sources
PubMed2006

Prenatal diagnosis of some metabolic diseases using early amniotic fluid samples: report of a 15 years, experience.

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.

Abortion, Spontaneous↗
PubMed2006

Contribution of fetal MR imaging in the prenatal diagnosis of Zellweger syndrome.

Zellweger syndrome (ZS), or cerebrohepatorenal syndrome, was the first described peroxisomal biogenesis disorder. It represents the most severe phenotype, and some of its multiple congenital anomalies can manifest prenatally. Fetal hypokinesia, renal hyperechogenicity, and cerebral ventricular enlargement are the most common reported fetal features. Single and/or late detectable manifestations account for most of the difficulties of prenatal diagnosis, as well as the limitations of ultrasonography itself. Prenatal diagnosis, however, can be achieved through (1) assays of concentrations of peroxisomal metabolites (very-long-chain fatty acids, bile acids, intermediates, plasmalogens), (2) activities of peroxisomal enzymes (dihydroacetone-phosphate acyltransferase), or (3) molecular screening techniques, if available. We report on the contribution of MR imaging to the diagnosis of ZS in 2 unrelated fetuses. MR imaging was performed in the third trimester because of cerebral ventricular enlargement diagnosed on routine sonography examinations. In both cases, MR imaging revealed ZS-characteristic abnormal cortical gyral patterns, impaired myelination, and cerebral periventricular pseudocysts. In addition, MR imaging revealed renal microcysts and hepatosplenomegaly in one case. The high level of resolution of MR imaging, which allows analysis of cerebral gyration and myelination, facilitates the prenatal diagnosis of complex polymalformative syndromes such as ZS.

Abortion, Eugenic↗
PubMed2005

Urea cycle defects: management and outcome.

This paper reviews the clinical presentation of 217 patients with urea cycle defects, including 121 patients with neonatal-onset forms and 96 patients with late-onset forms. Long-term outcome of these patients is also reported with the severity of the neonatal forms of these disorders, mostly for ornithine carbamoyltransferase-deficient males. Patients with late-onset forms may present at any age and carry a 28% mortality rate and a subsequent risk of subsequent disabilities.

Adolescent↗
PubMed2005

Severe hypoglycaemia in isolated 3-methylcrotonyl-CoA carboxylase deficiency; a rare, severe clinical presentation.

Since the introduction of neonatal screening for branched-chain organic acidurias, it has been noted that isolated 3-methylcrotonyl-CoA carboxylase deficiency is probably one of the most frequent organic acidurias. Only a few cases with severe clinical presentation have been described. Profound hypoglycaemia is an uncommon but life-threatening complication.

Carbon-Carbon Ligases↗
PubMed2005

Methylmalonic and propionic acidaemias: management and outcome.

Organic acidurias comprise many various disorders. Methylmalonic aciduria (MMA) and propionic aciduria (PA) are the most frequent diseases and the two organic acidurias for which we have better knowledge of the long-term outcome. Comparing the outcome of patients born before and after 1990, it appears that better neonatal and long-term management have improved the survival rate. Less than 20% of the patients died in either the neonatal period or before the age of 10 years. However, most surviving patients showed poor nutritional status with growth retardation and about 40% present some kind of visceral or neurological impairment. The developmental outcome may have improved in MMA patients, with IQ higher than 75 in about 40% patients aged more than 4 years. Conversely, poor intellectual development is the rule in PA patterns, with 60% having an IQ less than 75 and requiring special education. Successful liver and/or renal transplantations, in a few patients, have resulted in better quality of life but have not necessarily prevented neurological and various visceral complications. These results emphasize the need for permanent metabolic follow-up whatever the therapeutic strategy.

Child, Preschool↗
PubMed2004

Trends in serum citrulline and acute rejection among recipients of small bowel transplants.

A test for detecting acute cellular rejection (ACR) of small intestinal transplants (ITx) would be a major advance. Small preliminary studies suggest that serum citrulline levels correlate with ACR. The results for a group of 26 isolated intestinal and multivisceral transplant recipients are summarized here. Serum citrulline concentrations were determined by ion exchange chromatography and compared to biopsy-based grade of ACR. Other factors considered included patient and donor age and sex, ischemia time, and serum creatinine. Straight-line fits were employed to describe how each patient's citrulline levels changed over time. Estimated times to achieve normal citrulline (>or=30 micromol/L) ranged from 1 to 730 days posttransplant for 21 patients demonstrating increasing citrulline levels over time. Using stepwise linear regression, patients' ranks for time required to achieve normal citrulline levels were the only independent predictors of both maximum ACR (P <.0001) and average ACR (P =.0059) after 14 days posttransplant. The rate and direction of change in citrulline over time may be an indicator of the risk of acute rejection. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.

Adult↗
PubMed2004

Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria).

Succinic semialdehyde dehydrogenase (SSADH deficiency) (MIM 271980) is a defect in gamma-aminobutyric acid catabolism, resulting in the accumulation of gamma-hydroxybutyric acid (GHB) and causing neurological and cognitive disorders of varying severity. The non-specific nature and the difficulties in detection of urinary GHB explain why this disorder is largely underdiagnosed. Of 350 patients identified worldwide, to date only six adults with SSADH deficiency have been reported in the literature. Here we describe two additional cases in brothers up to ages 26 and 28 years. This retrospective report sheds light on the clinical features of SSADH deficiency in relation to the physiopathological involvement of GHB, and tries to identify the specific neurodevelopmental pattern of this learning disability.* Features of this are: early impaired psychomotor development with hypotonia and disturbances in motor coordination; impaired development of language, mainly due to poor auditory perception; and seizures and psychotic features in late adolescence or adulthood. Moreover, narcolepsy-like symptoms could be a consistent feature of the disease.

Adolescent↗
PubMed2002

Improving the prenatal diagnosis of citrullinemia using citrulline/ornithine+arginine ratio in amniotic fluid.

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.

Amniocentesis↗
PubMed2002

[Hematologic manifestations of inborn errors of metabolism].

Haematological symptoms can be helpful for the diagnosis of metabolic diseases. A megaloblastic anemia orientates to folate and cobalamine anomalies when associated with homocystinemia and decreased plasma methionine levels, or to congenital oroticuria (hypochromia), Pearson syndrome (sideroblasts and vacuolisation of precursors) and thiamine transporter abnormality (sideroblasts) in the absence of homocystinuria. An hemolytic anemia orientates to anomalies of anaerobic glycolysis, heme synthesis, or iron metabolism, and Wilson disease. A pancytopenia orientates to organic aciduria, lysinuric protein intolerance, mevalonic aciduria and lysosomal storage diseases (Gaucher, Niemann Pick, Wolman) when hepatosplenomegaly is present. Uremic hemolytic syndrome and hemophagocytic lymphohistiocytosis respectively orientate to B12 anomalies, lysinuric protein intolerance, lysosomal storage diseases and organic aciduria.

Child↗
PubMed2002

Plasma lysine concentration and availability of 2-ketoglutarate in liver mitochondria.

Defects of lysine metabolism are rare, but hyperlysinemia is a concomitant of many inborn errors of metabolism, including urea cycle abnormalities, pyruvate carboxylase deficiency and L-2-hydroxyglutaric aciduria. We have hypothesized that mitochondrial lysine degradation is regulated by bioavailability of 2-oxoglutarate in the same compartment, and our studies in physiologic fluid derived from patients with the above described disorders supports our hypothsis. Our data further suggest that patients with isolated L-2-hydroxyglutaric aciduria may have a defect in 2-ketoglutarate metabolism. The current report summarizes our studies.

Alanine↗
PubMed2002

Long-chain 3-hydroxyacylCoA dehydrogenase deficiency: a new case presenting with liver dysfunction, cholestasis and fibrosis.

UNLABELLED: A cholestatic 6-mo-old girl was admitted to our department because she recently presented with hypotonia and lethargy, apparently due to moderate and transient hypoglycaemia. Her urine contained 3-hydroxy-dicarboxylic acids of 12 to 14 carbons in length and her plasma acylcarnitine profile was consistent with long-chain 3-hydroxyacylCoA dehydrogenase deficiency. This diagnosis was confirmed by enzyme studies. This deficiency was due to a G1528C mutation on the paternal allele (mutation on the maternal allele as yet not identified). The patient improved dramatically with medium-chain triglyceride supplementation. CONCLUSION: Early cholestasis and hepatic fibrosis must lead to search for long-chain 3-hydroxyacylCoA dehydrogenase deficiency, particularly when hypoketotic hypoglycaemia is present.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2001

Combined nutritional support and continuous extracorporeal removal therapy in the severe acute phase of maple syrup urine disease.

OBJECTIVE: The authors assessed the efficiency, tolerance and outcome of neonates and children with maple syrup urine disease (MSUD) in acute decompensation managed by endogenous and extracorporeal removal of accumulated MSUD metabolites. DESIGN: Single center cohort study. SETTING: Pediatric and neonatal intensive care unit in a tertiary care hospital. PATIENTS: Between January, 1991, and June, 1999, six neonates and six children in acute decompensation of MSUD were included in the study. Each of them had two of the three following criteria: comatose state, gastrointestinal intolerance, leucine plasma levels over 1700 micromol/l. INTERVENTIONS: Patients were treated by combined nutrition manipulation and continuous venovenous extracorporeal removal therapies (CECRT) including hemofiltration, hemodialysis or hemodiafiltration. A clinical and biological evaluation was performed before, during and following the treatment. RESULTS: Eleven out of the 12 patients survived. One child had two acute episodes at 6.5 and 9 years old. Eight patients recovered a normal cerebral performance category score. In all cases, plasma leucine level decreased according to a logarithmic mode within 11-24 h hemodiafiltration combined with nutritional support whereas, with nutrition alone after stopping CECRT, the decrease in leucine plasma levels was slower, following a linear mode. Eight patients were supplemented with valine and isoleucine for mean plasma values of 177+/-92 and 68+/-66, respectively. CONCLUSION: In severe acute decompensation of MSUD, CECRT combined with nutritional support limit central nervous system damage, by dramatically decreasing branched chain amino and keto acid levels.

Acute Disease↗
PubMed2001

Serum citrulline and rejection in small bowel transplantation: a preliminary report.

BACKGROUND: There is no known serum marker for intestinal rejection. Serum concentrations of the amino acid citrulline arise almost exclusively from the intestinal mucosa. We examined the impact of acute cellular rejection (ACR) of intestinal allografts on serum citrulline levels. METHODS: Citrulline concentrations were assayed in serum samples of healthy volunteers (n=6) and seven patients who underwent small bowel transplants (SBTx). Trends in mean citrulline concentrations versus degree of ACR were assessed by matching posttransplantation citrulline concentrations with patients' grade of ACR at time of serum collection. Rejection was confirmed by biopsy and graded by following standardized criteria. An additional patient had citrulline concentrations determined for 31 sequential specimens 3-60 days posttransplant. RESULTS: Mean citrulline concentrations in controls were significantly higher than posttransplantation samples at any rejection grade. Mean concentrations declined significantly as rejection severity increased. The overall downward trend was statistically significant (P<0.05). In sequential measurements, citrulline levels increased significantly over time with declining severity of rejection. The increase in mean citrulline concentration between posttransplant days 3-16 and 52-60 was significant (P<0.01). CONCLUSIONS: Serum citrulline levels decline with increasing grade of ACR and may be a useful serum marker for intestinal rejection.

Adult↗
PubMed2001

Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350 m.

It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by reducing the availability of endothelial NO synthase (NOS III) substrate. To evaluate the effect of L-arginine on the NO release in high altitude, 11 subjects were infused with L-arginine (0.5 g x kg(-1)) during 30 min in normoxia and after 36 h at 4,350 m (hypoxia). The L-citrulline and cyclic guanosine monophosphate (cGMP) concentrations were measured to investigate NO synthesis and guanylyl cyclase activity respectively. L-citrulline concentration, arterial oxygen saturation (Sa,O2), systemic blood pressure, heart rate and acute mountain sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting infusion. The results showed that baseline L-citrulline was lower in hypoxia (p<0.05). L-arginine infusion increased L-citrulline concentration in both conditions. However, in hypoxia L-citrulline concentration remained lower than in normoxia (p<0.05). The concentration of cGMP was lower in hypoxia (p<0.05). In hypoxia, Sa,O2 increased from 15 min after the start of the infusion to 45 min (p<0.05). Blood pressure and heart rate were not affected by L-arginine infusion. Subjects who experienced symptoms of AMS showed a slight decrease in AMS score with L-arginine. The decreased L-citrulline suggests a hypoxia-induced impairment of nitric oxide synthase III or a decrease in L-arginine availability. The improvement of arterial oxygen saturation by pretreatment with L-arginine could be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively, these results are consistent with a decrease in nitric oxide production in hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.

Adult↗
PubMed2001

Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.

Hyperinsulinism and hyperammonemia syndrome has been reported as a cause of moderately severe hyperinsulinism with diffuse involvement of the pancreas. The disorder is caused by gain of function mutations in the GLUD1 gene, resulting in a decreased inhibitory effect of guanosine triphosphate on the glutamate dehydrogenase (GDH) enzyme. Twelve unrelated patients (six males, six females) with hyperinsulinism and hyperammonemia syndrome have been investigated. The phenotypes were clinically heterogeneous, with neonatal and infancy-onset hypoglycemia and variable responsiveness to medical (diazoxide) and dietary (leucine-restricted diet) treatment. Hyperammonemia (90-200 micromol/L, normal <50 micromol/L) was constant and not influenced by oral protein, by protein- and leucine-restricted diet, or by sodium benzoate or N-carbamylglutamate administration. The patients had mean basal GDH activity (18.3 +/- 0.9 nmol/min/mg protein) not different from controls (17.9 +/- 1.8 nmol/min/mg protein) in cultured lymphoblasts. The sensitivity of GDH activity to inhibition by guanosine triphosphate was reduced in all patient lymphoblast cultures (IC(50), or concentrations required for 50% inhibition of GDH activity, ranging from 140 to 580 nM, compared with control IC(50) value of 83 +/- 1.0 nmol/L). The allosteric effect of ADP was within the normal range. The activating effect of leucine on GDH activity varied among the patients, with a significant decrease of sensitivity that was correlated with the negative clinical response to a leucine-restricted diet in plasma glucose levels in four patients. Molecular studies were performed in 11 patients. Heterozygous mutations were localized in the antenna region (four patients in exon 11, two patients in exon 12) as well as in the guanosine triphosphate binding site (two patients in exon 6, two patients in exon 7) of the GLUD1 gene. No mutation has been found in one patient after sequencing the exons 5-13 of the gene.

Adolescent↗
PubMed2000

Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase.

delta(1)-pyrroline-5-carboxylate synthase (P5CS), a bifunctional ATP- and NADPH-dependent mitochondrial enzyme, catalyzes the reduction of glutamate to delta(1)-pyrroline-5-carboxylate, a critical step in the biosynthesis of proline, ornithine and arginine. Recently, we reported the cloning and expression of human and murine P5CS cDNAs. Previously, we showed that mammalian P5CS undergoes alternative splicing to generate two isoforms differing only by a 2 amino acid insert at the N-terminus of the gamma-glutamyl kinase active site. The short isoform has high activity in the gut, where it participates in arginine biosynthesis and is inhibited by ornithine. The long isoform, expressed in multiple tissues, is necessary for the synthesis of proline from glutamate and is insensitive to ornithine. Here, we describe a newly recognized inborn error due to the deficiency of P5CS in two siblings with progressive neurodegeneration, joint laxity, skin hyperelasticity and bilateral subcapsular cataracts. Their metabolic phenotype includes hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia. Both are homozygous for the missense mutation, R84Q, which alters a conserved residue in the P5CS gamma-glutamyl kinase domain. R84Q is not present in 194 control chromosomes and dramatically reduces the activity of both P5CS isoforms when expressed in mammalian cells. Additionally, R84Q appears to destabilize the long isoform. This is the first documented report of an inborn error of P5CS and suggests that this disorder should be considered in the differential diagnosis in patients with neurodegeneration and/or cataracts and connective tissue disease.

Adult↗