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Biomedical subjects

M Odièvre

Publications and source records attributed to M Odièvre.

At least 19 recordsLinked to original sources
PubMed2000

Genetic heterogeneity of glycogen storage disease type Ia in France: a study of 48 patients.

Forty-eight patients with glycogen storage disease type Ia (GSD Ia) were studied. Using a combination of single-strand conformation polymorphism (SSCP) analysis, restriction enzyme digestion and direct sequencing, we were able to identify 93/96 mutant alleles, comprising 23 different mutations in the glucose-6-phosphatase gene (G6PC). Among these, 7 are novel mutations of G6PC: M5R, T111I, A241T, C270R, F322L, and two deletions, 793delG and 872delC, resulting in the same mutation at the amino acid level, fs300Ter (300X).

Alleles↗
PubMed2000

[Prevention of vitamin D deficiency in adolescents and pre-adolescents. An interventional multicenter study on the biological effect of repeated doses of 100,000 IU of vitamin D3].

UNLABELLED: Recent studies have shown a high prevalence of calcium and vitamin D deficiencies in adolescents. The aim of this present study was to follow the changes in calcium status and 25 hydroxyvitamin D (25[OH]D) and parathyroid hormone (iPTH) levels during winter in preadolescents and adolescents from four university hospitals in northern France. SUBJECTS AND METHODS: Two groups of teenagers and adolescents (range: 10-15 years) were followed from October 1996 to June 1997. They were given either 100,000 IU of vitamin D (treated group n = 33) or a placebo (control group n = 35) in October, January and April. Serum calcium, phosphate, 25(OH)D and iPTH levels were measured at inclusion and every three months thereafter. RESULTS: At inclusion, plasma or serum 25(OH)D levels were < or = 10 ng/mL in 16 subjects and < 6 ng/mL in six. In control children, no significant change in 25(OH)D occurred during the study, while plasma or serum iPTH levels increased to 34 +/- 11 pg/mL. In the treated groups, 25(OH)D levels remained > 20 ng/mL in every subject; no hypercalcemia was observed; and the mean plasma or serum iPTH level was 25 +/- 14 pg/mL at the end of the study. CONCLUSION: Teenagers presented with a high prevalence of biological vitamin D deficiency at the end of summer. The increase of iPTH during winter in the unsupplemented group suggests that this has secondary consequences on their calcium homeostasis unless they are supplemented with vitamin D. We advocate a sufficient calcium supply and a 100,000 IU vitamin D supplement given two or three times during winter to preadolescents and adolescents living in northern France.

Adolescent↗
PubMed2000

Apolipoprotein E polymorphism and serum concentrations in patients with glycogen storage disease type Ia.

In patients with glycogen storage disease type Ia (glucose-6-phosphatase deficiency), serum triglyceride concentrations are markedly raised, whereas phospholipids and cholesterol levels are only moderately elevated. In addition, both VLDL and LDL lipoprotein fractions are raised. Despite these abnormalities, endothelial vascular dysfunction and atherosclerosis seem to be rare in such patients. In view of the crucial role of apolipoprotein E (apoE) in lipid metabolism, we studied both apoE polymorphism (40 patients) and serum concentration (20 patients) in patients with glycogen storage disease type Ia. The distribution of each allele at the apoE locus was similar to that reported in the general population, whereas serum apoE concentrations were raised in our patients. Raised apoE levels in the serum could play an important role in counterbalancing the at-risk-for-atherosclerosis lipid profile of patients with glycogen storage disease type Ia. Moreover, E3 and E4 polymorphisms, predominant in our patients, have a high triglyceride binding capacity and are thus able to increase triglyceride clearance. However, the origin of raised concentrations of apoE is not completely clear though, bearing in mind previous reports regarding serum protein concentrations in such patients, increased hepatic synthesis is likely.

Adolescent↗
PubMed1999

Molecular cloning, expression and physical mapping of the human methionine synthase reductase gene.

Methionine synthase reductase (EC 2.1.1.135) is a flavoprotein essential for maintenance of methionine synthase in an active state. We characterized the human gene for methionine synthase reductase (MTRR). The gene is approximately 34kb and comprises 15 exons, varying in size from 43 to 1213bp, and 14 introns whose sizes vary from 108bp to 5kb. The positions of several junctions are conserved between the MTRR gene and the C. elegans ortholog, as well as with the rat cytochrome P450 reductase gene. A 1.3kb CpG island encompasses the 5'-flanking region and exon 1 and extends into intron 1. A short region including the transcription start site is sufficient to confer promoter activity, with a better outcome when accompanied by intron 1. The promoter region contains putative binding sites for Sp1, AP-1, AP-2 as well as CAAT motifs, but no consensus TATA box. Primer extension analysis revealed a single major transcription start site, located 137bp upstream of the previously reported initiator ATG. An alternative splicing event involving a portion of exon 1 predicts that translation can potentially be initiated at two different ATG codons. The gene was physically assigned to a narrow area between markers WI1755 and D5S1957.

Animals↗
PubMed1999

Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency.

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1999

Jaundice with hypertrophic pyloric stenosis as an early manifestation of Gilbert syndrome.

Jaundice associated with hypertrophic pyloric stenosis was recognised in three patients; previous reports have suggested that this is a possible early manifestation of Gilbert syndrome. Most patients with Gilbert syndrome are homozygous for a (TA)(7)TAA polymorphism in the gene promoter coding for bilirubin glucuronosyltransferase. Two of the reported patients were homozygous for the (TA)(7)TAA polymorphism whereas the third was heterozygous for the same polymorphism. Furthermore, no other factors contributing to jaundice in the three patients were found. These results suggest that jaundice associated with hypertrophic pyloric stenosis is due to molecular defects within the gene promoter.

Adult↗
PubMed1998

Prenatal diagnosis of glycogen storage disease type Ia by restriction enzyme digestion.

Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive condition, caused by a deficiency of hepatic glucose-6-phosphatase (G6Pase) activity. In a consanguineous family originating from northern Africa whose first daughter was affected with GSD Ia, we were able to identify the disease-causing mutation, a cytosine to thymine substitution at nucleotide 326 in exon 2 of the G6Pase gene (R83C). This mutation causes the disappearance of an HgaI site, and is thus easily detectable by restriction enzyme digestion. Both parents were heterozygous for this mutation. During the third pregnancy, fetal genomic DNA was extracted from a chorionic villus biopsy sampled at the 24th week of gestation. Exons 2 of the G6Pase gene were amplified by the polymerase chain reaction followed by HgaI digestion. Fetal DNA analysis indicated that the fetus had received both normal G6Pase alleles. This result was confirmed after birth. DNA analysis is the only reliable method for prenatal diagnosis of GSD Ia.

Consanguinity↗
PubMed1997

[Vae soli!].

Explore the source record for details and available documents.

France↗
PubMed1997

Hepatocellular adenomas in glycogen storage disease type I and III: a series of 43 patients and review of the literature.

BACKGROUND: Hepatocellular adenomas may develop in patients with glycogen storage disease types I and III, and the malignant degeneration of adenomas in hepatocellular carcinoma has been reported in ten cases. The aim of this work was to study the characteristics of hepatic adenomas in a large series of 43 patients with glycogen storage disease types I and III and to determine the optimal means of follow-up. METHODS: The charts of 43 patients with glycogen storage disease type I and III were studied. In all these patients, abdominal ultrasonography and the determination of serum alpha-fetoprotein had been performed yearly and serum concentrations of several proteins were determined once. RESULTS: 51.8% of patients with type I and 25% of patients with type III glycogen storage disease had hepatic adenomas at the time of the study. The male to female ratio was 2 to 1 in type I, and no female had adenomas in type III. No evidence of malignant transformation was observed during the follow-up period. Serum concentrations of several proteins were significantly higher in patients with hepatic adenomas than in patients without such lesions. CONCLUSIONS: In patients with glycogen storage disease type I and III, the determination of alpha-fetoprotein serum concentration has to be combined with yearly hepatic ultrasound examinations. Other investigations such as CT scan should be considered when the size of any adenoma increases. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma remains a rare event.

Adenoma, Liver Cell↗
PubMed1996

Current therapy for Crigler-Najjar syndrome type 1: report of a world registry.

This study represents a multicenter survey on the management of patients with Crigler-Najjar syndrome (CNS) type 1. The aim of the survey was to find guiding principles for physicians in the care of these patients. Fifty-seven patients were included. At the time of inclusion, 21 patients had received a liver transplant (37%). The average age at transplantation was 9.1 +/- 6.9 years (range, 1-23 years); the age of the patients who had not been transplanted at the time of inclusion was 6.9 +/- 6.0 years (range, 0-23 years). Brain damage had developed in 15 patients (26%). Five patients died, and 10 are alive with some degree of mental or physical handicap. In 2 patients, ages 22 and 23 years, early signs of bilirubin encephalopathy could be reversed, in 1 by prompt medical intervention followed by liver transplantation and in the other by prompt liver transplantation. Seven patients underwent transplantation with some degree of brain damage at the time of the surgery; 1 of these died after retransplantation, 2 improved neurologically, and 4 remained neurologically impaired. The age of 8 patients with and 13 without brain damage at or before transplantation was 14.3 +/- 5.9 and 5.9 +/- 5.4 years (P < .01), respectively. Therapy of CNS type 1 consists of phototherapy (12 h/d), followed by liver transplantation. Phototherapy, although initially very effective, is socially inconvenient and becomes less efficient in the older age group, thus also decreasing compliance. Currently, liver transplantation is the only effective therapy. This survey shows that, in a significant number of patients, liver transplantation is performed after some form of brain damage has already occurred. From this, one must conclude that liver transplantation should be performed at a young age, particularly in situations in which reliable administration of phototherapy cannot be guaranteed.

Adolescent↗
PubMed1995

[Vitamin D and pubertal maturation. Value and tolerance of vitamin D supplementation during the winter season].

BACKGROUND: In France, several cases of vitamin D-deficiency rickets among adolescents have been reported, but no prophylaxis measure has been systematically recommended at this age. The aim of this study was to measure 25-hydroxyvitamin D (25-(OH)D) levels and to search for biological signs of vitamin D deficiency during adolescence. Moreover, the effects of a unique oral dose of 100,000 IU of vitamin D3, given during the winter, were analysed. POPULATION AND METHODS: Circulating levels of 25-(OH)D, 1,25-dihydroxyvitamin D, intact parathyroid hormone (iPTH), alkaline phosphatase activities, calcium and phosphate were measured in 53 adolescents aged 10-17 years (81% of metropolitan origin), seen during the winter. The effect of a single oral dose of 100,000 IU of vitamin D3 or of placebo was studied in 15 of these subjects. RESULTS: 24.5% of the adolescents had low 25-(OH)D concentrations (< 6 ng/ml), this frequency being even more elevated (38%) at the end of pubertal maturation (stages 4 and 5). An increase in iPTH concentrations was found in subjects with lowest 25-(OH)D levels (< 3 ng/ml). An oral dose of 100,000 IU of vitamin D3 resulted in a significant increase in the 25-(OH)D levels; yet, these levels remained within the normal range during the 1-2 month follow-up of the nine treated subjects. This dosage made it possible to correct the low calcium concentrations (2.20-2.24 mmol/l) found before treatment in three adolescents. CONCLUSIONS: The high frequency of low vitamin D status observed during puberty and its normalization after a 100,000 IU vitamin D3 supplementation show the interest and safety of this intermittent 100,000 IU vitamin D3 supplementation to adolescents during the winter season.

Adolescent↗
PubMed1995

[Acute lipid pneumopathy].

BACKGROUND: Lipid pneumonia in children has rarely been described in Europe. In some countries, due to local customs, the course is chronic. This study describes an acute lipid pneumonia in a young boy. CASE REPORT: A 12 year-old boy, previously treated for a rhabdomyosarcoma, developed acute fever with thoracic pain. A chest radiograph revealed heterogenous consolidation. The patient was given oral antibiotics, although no improvement was observed. The diagnosis of lipid pneumonia was made by a bronchoscopy with bronchoalveolar lavage. Treatment with corticosteroids was started. Clinical manifestations improved rapidly. One month later, chest radiograph and biological findings were normal. CONCLUSION: Diagnosis of lipid pneumonia should be considered in children with an acute febrile pneumonitis non resolving with antibiotic treatment. Examination of the fluid obtained by bronchoalveolar lavage confirms the diagnosis.

Acute Disease↗
PubMed1995

Mutations in the phosphorylase kinase gene PHKA2 are responsible for X-linked liver glycogen storage disease.

Phosphorylase kinase (PHK) is a key enzyme in the control of glycogen breakdown. Several types of PHK deficiency have been described of which X-linked liver glycogenosis type I (XLG I) is the most common. Since the XLG I locus and the gene encoding the liver alpha-subunit gene of PHK (PHKA2) have both been localized to Xp22, PHKA2 was a candidate gene for XLG I. In this study we identified four point mutations in four unrelated XLG I patients: three mutations introduce a premature stop codon, whereas the fourth mutation abolishes a splice site consensus sequence leading to exon skipping. These findings indicate that PHKA2 is the XLG I gene.

Base Sequence↗