PubMed Health⌕ Search

Biomedical subjects

J Berthelot

Publications and source records attributed to J Berthelot.

At least 19 recordsLinked to original sources
PubMed2006

D-2-hydroxyglutaric aciduria in three patients with proven SSADH deficiency: genetic coincidence or a related biochemical epiphenomenon?

Succinic semialdehyde dehydrogenase (SSADH) deficiency and D-2-hydroxyglutaric aciduria (D-2-HGA) are rare inborn errors of metabolism primarily revealed by urinary organic acid screening. Three patients with proven SSADH deficiency excreted, in addition to GHB considerable amounts of D-2-HG. We examined whether these patients suffered from two inborn errors of metabolism by measuring D-2-HG concentrations in the culture medium of cells from these patients. In addition, mutation analysis of the D-2-hydroxyglutarate dehydrogenase gene was performed. Normal concentrations of D-2-HG were measured in the culture media of fibroblasts or lymphoblasts derived from the three patients. In one patient, we found a heterozygous likely pathogenic mutation in the D-2-hydroxyglutarate dehydrogenase gene. These combined results argue against the hypothesis that the patients are affected with "primary" D-2-HGA in combination with their SSADH deficiency. Moderately increased levels of D-2-HG were also found in urine, plasma, and cerebrospinal fluid samples derived from 12 other patients with SSADH deficiency, revealing that D-2-HG is a common metabolite in this disease. The increase of D-2-HG in SSADH deficiency can be explained by the action of hydroxyacid-oxoacid transhydrogenase, a reversible enzyme that oxidases GHB in the presence of 2-ketoglutarate yielding SSA and D-2-HG.

Alcohol Oxidoreductases↗
PubMed2005

[Management of phenylketonuria and hyperphenylalaninemia: the French guidelines].

Phenylketonuria (PKU) is an inherited metabolic disease affecting about one birth out of 15 000. From 1978, a national systematic neonatal screening was set up in France with a regional organisation. French rational and guidelines have been established by the national PKU group with the collaboration of all the physicians responsible for the regional centres. These guidelines specify the minimal diagnosis procedures leading to an optimal treatment of all patients. A low-phenylalanine diet must be started as soon as possible in the neonatal period for all newborns whose phenylalanine levels are above 10 mg/dl. The dietary control must keep the phenylalanine plasma levels between 2 and 5 mg/dl until 10 years of age. After this age, several data argue for a progressive and controlled relaxation of the diet, keeping the phenylalanine level below 15 mg/dl until the end of the adolescence and below 20 to 25 mg/dl in adulthood. All PKU patients must be followed up for life, in order to screen those who may not bear the diet relaxation and in order to strictly prevent maternal PKU deleterious consequences.

Child↗
PubMed2004

[Mitochondrial cytopathy: an unusual infantile cause of total villous atrophy].

Villous atrophy in an infant immediately suggests food intolerance. We report a case with an unusual cause. This female infant was first examined at 5 months for anorexia and failure to thrive. Intestinal biopsy showed total villous atrophy. A diet excluding gluten and cow milk proteins failed to improve her condition and the infant was hospitalized at 7 months for further investigations. The infant was hypotonic with a head lag. No other clinical sign was noted. Serum transaminases were increased 5- to 10-fold and CSF proteins concentration was increased. Metabolic investigations revealed hyperlactacidaemia and an increased lactate/pyruvate ratio during fasting and feeding, suggesting a mitochondrial cytopathy. Respiratory chain enzymatic activity measurements confirmed the diagnosis and showed severely decreased activities of complexes I, III and IV in both the liver and muscle. Molecular analysis demonstrated depletion of mitochondrial DNA in the liver (75%) and in muscle (97%). The infant was discharged under continuous enteral nutrition. Improvement was of short duration and the infant died at 1 year of age of massive hepatic failure. This is the first report of a mitochondrial DNA depletion with total villous atrophy and malabsorption as early clinical onset. A mitochondrial cytopathy should be considered in such conditions when food exclusion diets fail.

Atrophy↗
PubMed2001

Neonatal screening and long-term follow-up of phenylketonuria: the French database.

BACKGROUND: In France, neonatal screening of phenylketonuria (PKU) started in 1966. A national association was created in 1978 in order to organise the neonatal screening program and to control the efficacy of the screening and patients' follow-up. AIMS: To evaluate the results of the French PKU screening program in terms of hyperphenylalaninaemia epidemiology, efficacy of the screening procedure, management and outcome of the patients. STUDY DESIGN: The national database has been filled-up first with the answers to questionnaires that were sent each year by the PKU patients' physicians, and second with the results of an additional inquiry, which was set up in 1994 in order to investigate diagnosis, treatment, and school outcome of all French PKU patients. RESULTS: PKU was diagnosed in 81.6% of patients with hyperphenylalaninaemia (HPA), non-PKU HPA in 17.2% and cofactor deficiency in 1.1%. From 1980, incidence of PKU has been stable: 1 per 17,124 live births. Sensitivity of the screening procedure was 99.3%. Age at diet initiation regularly decreased to reach 14 days as a median in 1996. Until 1990, median age at diet discontinuation was 6 years of age. Later, strict diet was continued longer (at least, up to 8-10 years). PKU patients who entered to secondary school at normal age were characterised by an earlier age at diagnosis and at diet initiation and a later age at diet discontinuation, compared to those who entered 1 year or more behind normal age. CONCLUSION: These data confirm the benefit of a nationwide organised screening program. They emphasise the importance of an early neonatal diagnosis and diet initiation in PKU patients and are consistent with the benefit of a longer period of strict diet in childhood.

Child↗
PubMed2001

Echocardiographic assessment of the interventricular delay of activation and correlation to the QRS width in dilated cardiomyopathy.

The aim of the study was to define criteria for left ventricular pacing in dilated cardiomyopathy (DCM) using an echocardiographic evaluation of interventricular electromechanical delay (IMD) and a correlation of IMD to QRS duration. Standard 12-lead ECG and echocardiography with pulsed Doppler tissue imaging (DTI) were recorded in 35 DCM patients (mean age 58 +/- 11 years) with QRS duration from narrow (80 ms) to broad (222 ms) patterns. The timefor left ventricular activation was evaluated from the onset of QRS to the onset of aortic flow (Q-Ao) by standard pulsed Doppler (SP) or to the onset of mitral annulus systolic wave (Q-Mit) (DTI). The time for right ventricular activation was determinedfrom the onset of QRS to the onset of pulmonary flow (Q-Pulm) (SP) or to the onset of tricuspid annulus systolic wave (Q-Tri) (DTI). (Q-Ao)-(Q-Pulm) and (Q-Mit)-(Q-Tri) determined IMD for each method, respectively. QRS width and IMD showed correlation coefficients of r = 0.86 ([Q-Ao]-[Q-Pulm]) and r = 0.82 ([Q-Mit]-[Q-Tri]) (P < or = 0.001 ). Mean IMD of 77 +/- 15 ms (SP) and 88 +/- 26 ms (DTI) were noted for QRS width above 150 ms. Left ventricle delayed activation was positively correlated to QRS widening with both methods, (r = 0.90, [Q-Ao]), (r = 0.83, [Q-Mit]) (P < or = 0.001). In conclusion, QRS duration is a good marker of an interventricular mechanical asynchrony. According to IMD correction, left ventricular pacing may be mainly proposed to symptomatic DCM patients with QRS duration > 150 ms.

Adult↗
PubMed1999

Blood concentrations of pancreatitis associated protein in neonates: relevance to neonatal screening for cystic fibrosis.

AIM: To determine whether pancreatitis associated protein (PAP) is a marker for cystic fibrosis which could be used in neonatal screening for the disease. METHODS: PAP was assayed on screening cards from 202,807 neonates. Babies with PAP > or = 15 ng/ml, or > or = 11.5 ng/ml and immunoreactive trypsinogen (IRT) > or = 700 ng/ml were recalled for clinical examination, sweat testing, and cystic fibrosis transmembrane regulator (CFTR) gene analysis. RESULTS: Median PAP value was 2.8 ng/ml. Forty four cases of cystic fibrosis were recorded. Recalled neonates (n = 398) included only 11 carriers. A receiver operating characteristic curve analysis showed that PAP above 8.0 ng/ml would select 0.76% of babies, including all those with cystic fibrosis, except for one with meconium ileus and two with mild CFTR mutations. Screening 27,146 babies with both PAP and IRT showed that only 0.12% had PAP > 8.0 ng/ml and IRT > 700 ng/ml, including all cases of cystic fibrosis. CONCLUSION: PAP is increased in most neonates with cystic fibrosis and could be used for CF screening. Its combination with IRT looks promising.

Acute-Phase Proteins↗
PubMed1998

[Dorfman-Chanarin syndrome].

BACKGROUND: Dorfman-Chanarin syndrome is an uncommon condition characterized by non-bullous congenital ichtyosiform erythrodermia and lipid vacuoles in circulating leukocytes. CASE REPORT: We report an unusual presentation in a child who had a dry congenital ichtyosiform erythroderma. Blood smears revealed lipid vacuoles in granulocyte cytoplasm, leading to the diagnosis of Dorfman-Chanarin syndrome. The child also had liver and ophthalmologic involvement. DISCUSSION: Dorfman-Chanarin syndrome is a rare autosomic recessive hereditary disease (27 cases reported in the literature) related to the accumulation of neutral lipids in organ tissues. Clinical manifestations are dry congenital ichtyosiform erythroderma and lipid vacuoles in circulating granulocytes. The syndrome may be expressed more or less severely in several organs. Diagnosis is confirmed on blood smears. The vacuoles can also be observed in smears of heterozygous subjects and can serve as a screening test. The pathogenesis of Dorfman-Chanarin syndrome is poorly understood but appears to be related to perturbed intracellular triglyceride catabolism. Treatment is symptomatic.

Child, Preschool↗
PubMed1993

X-linked liver glycogenosis: localization and isolation of a candidate gene.

X-linked phosphorylase kinase (PHK) deficiency causes X-linked liver glycogenosis (XLG) which is the most frequent liver glycogen storage disorder in man. Recently we assigned XLG to the Xp22 chromosomal region by linkage analysis in two families segregating XLG. In this study a further localization of XLG in Xp22 was performed by extending the number of Xp22 markers, by extension of the number of family members from the two families of our previous study and by linkage analysis in four additional XLG families. Two-point linkage analysis revealed lod scores of 4.60, 5.73, 5.28, 8.62 and 5.14 for linkage between XLG and the DNA markers pXUT23 and pSE3.2-L(DXS16), pD2(DXS43), pTS247-(DXS197) and pPA4B(DXS207), respectively, all at 0% recombination. Linkage heterogeneity was not observed in this set of families. Multipoint linkage analysis increased the lod score for linkage between XLG and Xp22 to 16.79 relative to DXS197/DXS207. The position of the XLG gene was confirmed by analysis of recombinational events locating the XLG gene between DXS85 and DXS41. The XLG gene could not be mapped more precisely in this chromosomal region of approximately 20cM because of the absence of recombinational events between the XLG gene and the Xp22 markers. As we have previously shown that the rabbit liver alpha subunit of PHK (PHKA2) hybridizes to human Xp22, we isolated a human PHKA2 cDNA from a human hepatoma lambda gt11 cDNA library. Fluorescent in situ hybridization mapped human PHKA2 to Xp22. As this physical mapping coincides with the genetic mapping of XLG by linkage analysis, PHKA2 most probably harbours the mutation(s) responsible for XLG.

Amino Acid Sequence↗
PubMed1992

Time and space clusters of the French-Canadian M1V phenylketonuria mutation in France.

We performed mutation analysis and RFLP haplotype analysis of chromosomes associated with classical phenylketonuria (PKU) in contemporary French families. We also did genealogical reconstructions for seven obligate carriers in five contemporary French-Canadian families living in eastern Quebec, who carry the M1V mutation causing PKU. The M1V mutation, heretofore considered to be associated exclusively with French-Canadians, was found on 4 of 152 independent French chromosomes. The French and Quebec M1V mutations all occurred on RFLP haplotype 2. The contemporary mutant French chromosomes clustered in southern Brittany (Finistère Sud). Genealogical reconstructions of the Quebec families identified 53 shared ancestors and a center of diffusion in the Perche region in 17th century France. The two clusters in France, one historical and the other contemporary, are not incompatible, if one assumes the possibilities that settlers returned from Nouvelle France or moved from Perche to southern Brittany. The M1V mutation is serving as a useful marker for historical demography.

Base Sequence↗
PubMed1991

Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene.

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle in humans and is responsible for lethal neonatal hyperammonemia in males. Partial OTC deficiency also occurs in females and can be responsible for life-threatening hyperammonemic comas in heterozygotes. The cosegregation of the trait with a 5.8-kb abnormal MspI fragment in an affected family led us to hypothesize that this unexpected migration pattern was related to the mutation event in this particular family. Using polymerase chain reaction amplification of the specific mRNA derived from a post-mortem biopsy of the liver, we found that the MspI site located in the seventh exon of the gene was abolished and we finally identified a C-to-T transition at codon 225 of the cDNA, changing a proline to a leucine in the protein. Subsequent digestion of amplified exon 7 using the restriction enzyme MspI allowed direct screening for the mutant genotype during the next pregnancy. The present study supports the view that direct detection of the mutant genotype using either Southern blotting or digestion of amplified exons of the gene can contribute to genetic counselling in noninformative families. Finally, since MspI digestions are routinely performed for restriction fragment length polymorphism-based family studies in OTC deficiency, we suggest that the possible presence of the 5.8-kb abnormal fragment should be investigated on Southern blots of affected individuals.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

A probable sex difference in mutation rates in ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency is an X-linked disease with possible manifestations in heterozygous females. Using segregation analysis in families from the literature pooled with a French series, the penetrance could be estimated to be 17% in heterozygous females (15% with severe and 2% with milder symptoms). Using these estimates, the proportion of sporadic cases among heterozygous females and hemizygous males could be derived. This proportion is 57% in females. In males, it depends on mutation rate values: assuming equal mutation rates in sperm and eggs, this proportion should be 40%. However, this value can be strongly rejected based on the proportion of isolated cases in male sibships. In both sets of data, segregation analysis provided no evidence for sporadic affected males, suggesting that there are virtually no mutations in eggs. The upper limit of the confidence interval, 0%-16%, can be taken as the maximum prior probability that an affected male occurs as the result of a new mutation in his mother's germ cells.

Female↗
PubMed1990

[Congenital cutaneous aplasia of the scalp. Apropos of 4 cases].

Report of four cases of congenital defects of the scalp. In two of these cases, the skin defect was associated with a skull defect and in one, there were other cranial deformities. In each case, the lesion seemed isolated in otherwise normal children. This study contains a review of congenital scalp defects. The different aspects of this rare disease are presented and the treatment is discussed with reference to natural evolution. The authors differentiate between cases with isolated lesion and cases with associated malformations or abnormalities, malformation syndromes, as has been previously defined. In the case of skull defects, it is thought that immediate reparatory surgery must be performed, to prevent infection and hemorrhage of sagittal venous sinus, as it was the case in one of the four children. The covering of the defect can be realized with rotated skin flaps, which seem preferable to any form of plastic surgery, for cosmetic reasons, and for the secondary treatment of the skull defect, if this is necessary. When spontaneous closure of the bone defect, is not noted, which occurs generally in the case of large defects, it seems reasonable to close the latter by cranio-plasty, to protect the brain. In one of the four cases reported, this technical approach of the lesion was used, with a good result being reported, four years later.

Calcinosis↗
PubMed1980

[Diabetic ketoacidosis with severe hypertriglyceridemia and eruptive xanthomata (author's transl)].

A boy of 6 with diabetic ketoacidosis presented with a disturbance of lipid metabolism characterised by eruptive xanthomata, hepatomegaly, lipaemia retinalis, milky serum and hypertriglyceridemia with type V electrophoretic pattern. All the findings are typical diabetic hyperlipidaemia. The severity of the abnormalities are not solely due to delay in treatment because they are also caused by the unusual sensitivity of lipoprotein lipase to insulin deficiency. A histological and ultrastructural study of the xanthomata was performed.

Child↗
PubMed1978

[Rudiger (E. E. C.) syndrome: report of a case associated with atopic dermatitis (author's transl)].

The syndrome of ectrodactyly, ectodermal dysplasia and cleft lip-palate is described in a boy aged 3; although inherited in most cases as an autosomal dominant trait, it seems here to be sporadic. An atopic dermatitis clinically evident and particularly resistant to treatment is present, but IgE level is not raised. Ophthalmologic changes are prominent. Systematic intravenous pyelogram showed urinary tract strictures.

Child, Preschool↗
PubMed1977

[Krabbe's disease].

Explore the source record for details and available documents.

Clinical Enzyme Tests↗