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J L Dhondt

Publications and source records attributed to J L Dhondt.

At least 19 recordsLinked to original sources
PubMed2003

Neonatal screening for cystic fibrosis: France rises to the challenge.

This paper describes the adjustments to the French neonatal screening programme required by the introduction of systematic screening for cystic fibrosis (CF), taking into account both the legal and statutory framework and the lessons of a pilot study carried out 10 years ago. The French association for the screening and prevention of infant handicaps (AFDPHE) has been mandated by its regulatory agencies to organize screening for CF in France (metropolitan and overseas territories). During the year 2001, expert groups (Technical Aspects, Information, Ethics and Genetics, Criteria for CF Centres, Protocol for the Care of a Newborn with CF) issued recommendations for the establishment of a national programme that would guarantee efficiency and adequate patient care from the time of diagnosis onward. The programme is based on a strategy combining immunoreactive trypsin (IRT) assay and the analysis of DNA mutations in dried blood samples obtained at 3 days of age. When an elevated IRT value is found, DNA analysis is performed on the same sample. Owing to the relative regional heterogeneity existing in France, 30 selected mutations are used, which provide 85% coverage. The Ethics and Genetics Committee recommended that, in order to avoid arousing anxiety by a recall, informed consent, according to the French legislation on bioethics, should be obtained for all neonates at birth by having the parents sign directly on the sampling paper. Information brochures for parents and health professionals have been designed. A new organization of patient care, involving the creation of CF centres recognized by the Ministry of Health, has been decided; all children diagnosed are to be referred to such centres, where they can be well cared for by a trained staff with sufficient means. The programme was implemented region by region in France, from the beginning of the year 2002 to early 2003. The expert groups still meet periodically to evaluate the implementation of the programme and to check that the terms of the agreement between the AFDPHE and the Social Security Agency are complied with.

Cystic Fibrosis↗
PubMed2003

[Sickle cell disease neonatal screening. First evaluation].

A neonatal screening allows a preclinical diagnosis of major sickle cell syndromes and an early management of the affected children. That would improve their life quality and expectancy. The preliminary program was set up on 518 senegalese newborn aged from 1 to 4 days, and coming from all the country ethnic groups. Isoelectrofocalisation is the test used on dried blood eluate and the positive control on citrate agar gel. 478 samples out of 518 (92.5%) have been analysed. Haemoglobinopathy have been found in 11.1% of cases, distributed as follow: heterozygoty FAS and FAC: 9%, double heterozygoty FSC: 0.2% and homozygoty FSS: 1.9%. Sickle cell neonatal screening should be imperatively implemented, with regards in economical considerations. It would be relevant to integrate it in a larger program including information, training and genetic counselling in order to avoid homozygotes birth and to lower the spread of this disease.

Anemia, Sickle Cell↗
PubMed2000

Clinical and EEG video-polygraphic features of epileptic spasms in a child with dihydropteridine reductase deficiency. Efficiency of hydrocortisone.

West syndrome is an epileptic encephalopathy which includes psychomotor deterioration. In rare cases, it is due to an inherited, progressive metabolic disease. We report a 2 year-old child with dihydropteridine reductase deficiency who developed hypsarrhythmia and infantile spasms which were documented on video-polygraphic EEG. Despite dietary restriction of phenylalanine, and oral administration of amine precursors, the initial course was unfavorable. A beneficial effect from hydrocortisone was then observed, with control of spasms and improvement of psychomotor delay.

Anti-Inflammatory Agents↗
PubMed1999

[Progressive convulsive encephalopathy: considering a abnormality of biopterin metabolism].

BACKGROUND: Symptomatic forms of hyperphenylalaninemia are rare in France since neonatal screening began. CASE REPORT: A child born in Algeria from consanguinous parents was referred at 2 years of age for a severe epileptic encephalopathy with hypotonia. Amino acid chromatography revealed hyperphenylalaninemia due to a dihydropteridine reductase deficiency. Dietary restriction of phenylalanine and oral administration of amine precursors, L-dopa and 5-hydroxytryptophan had poor efficiency on epilepsy and psychomotor delay. CONCLUSION: Diagnosis of hyperphenylalaninemia must be evoked in any children with progressive encephalopathy born in country where neonatal screening is not performed.

5-Hydroxytryptophan↗
PubMed1999

Quality assurance and standardization: summary of the satellite meeting, Turku, Finland, 11-12 June 1999.

The Quality Assurance (QA) and Standardization satellite meeting addressed five major issues in newborn screening: (i) Pre- and post-analytical phases are important in the overall quality of screening, and quality assurance programs should include these aspects. (ii) It is possible to run a single screening program using laboratories on more than one site, as is done in Europe, California and Cuba. Special quality assurance procedures are necessary for success. (iii) It is possible to achieve improved analytical quality and international comparison of results by use of common reference materials such as the amino acid materials developed in Europe and the US. It will be important to use tested paper with defined performance characteristics. (iv) It is appropriate for newborn screening programs to be accredited, but it will also be important to develop criteria for pre- and post-analytic phases of screening. (v) A new QA program is being developed for Latin America. The Australasian QA program now includes amino acids and acylcarnitines in a form suitable for tandem mass spectrometry blind QA. The European Society for Paediatric Endocrinology has developed guidelines for CAH screening.

Accreditation↗
PubMed1998

Preparation of the first European working standard for phenylalanine determination in dried blood spots.

OBJECTIVE: To develop a standard preparation for measurement of phenylalanine in blood spots in phenylketonuria against which manufacturers of kits for phenylalanine determination could calibrate their own blood spot calibrators. METHODS: As most of the variation of phenylalanine concentration in dried blood spots is due to the way the blood spot calibrators are prepared, a minimum set of prerequisites for the preparation of blood spot calibrators was established by a group of scientific experts and manufacturers. A "European working standard for phenylalanine in blood spots" (EWS-Phe-01) was prepared and distributed to manufacturers taking part in this project. RESULTS: The control of the homogeneity, linearity, and stability of the EWS-Phe-01 batch gave results within expected ranges. The preliminary results of the recalibration of calibrators for phenylalanine against EWS-Phe-01 by the participating manufacturers were promising; the differences between measurements were much decreased. CONCLUSION: Manufacturers have agreed to use EWS-Phe-01, and since November 1996 EWS-Phe calibrators have been routinely available from these companies. This pilot study may act as a model for minimising discrepancies found in other screening tests.

Blood Chemical Analysis↗
PubMed1998

Dihydropteridine reductase deficiency in a large consanguineous Tunisian family: clinical, biochemical, and neuropathologic findings.

We report the case of a large consanguineous Tunisian family of seven siblings suffering from dihydropteridine reductase deficiency with either typical clinical, biochemical, or autopsy findings. Two cousins also were reported to have the same symptoms. This metabolic disorder is characterized by severe microcephaly, psychomotor regression, and progressive basal ganglia calcifications. Dihydropteridine reductase assay on samples collected from the two brothers still alive did not show measurable activity. The sister and four brothers died between the ages of 3 years and 7 years. A neuropathology study done on the sister showed diffuse demyelination throughout the white matter and spongy vacuolation in the subthalamic nuclei, the superior cerebellar peduncles and the tegmentum tracts of the brain stem. The anterointernal part of the putamen was completely necrotic with nearly total nerve cell loss. Abnormal vascular proliferation and calcification of the walls of small, medium, and large arteries and veins, as well as diffusely scattered pericapillary and isolated calcospherites, were seen in this necrotic region. We think that folate deficiency may be involved in the pathogenesis of the basal ganglia calcification.

Basal Ganglia Diseases↗
PubMed1997

[Iodine deficiency in the Cirque of Salazie (Reunion Island). Analysis of nutritional causes and study of their consequences].

Randomized subjects (n = 294), (35 young children, 6-30 months old--91 children 8.6 +/- 0.7 years, 116 teenagers 13.2 +/- 1.9 y--52 young women 28.5 +/- 6.1 y) leaving in a mountainous area of Reunion Island (Cirque de Salazie) were evaluated according to the following: a questionnaire related to food intake, cervical palpation for thyroid size evaluation and collections of urine and foods (natural and mineral water, breast and commercial milk and salt) for iodine measurement. Neonatal TSH of 308 new borns in Salazie were compared to TSH of 300 new-borns of Lille (France). The prevalence of goiter increases with age (0% in young children, 12.1% in children, 23.3% in teenagers, 38.4% in women) whereas median urinary iodine (microgram/dl) decreases in the same groups (12-7.8-5.6-4.2). The intake of milk and dairy products significantly decreases from children to adults. Neonatal TSH values are significantly higher in Salazie than in Lille (p < 0.005). Natural and mineral water, breast milk and salt contain little iodine. In conclusion iodine deficiency is present in this area of Reunion Island with a significant increment of neonatal TSH values.

Adolescent↗
PubMed1996

Need for a standardized procedure in the preparation of phenylalanine calibrators.

INTRODUCTION: Sensitive screening for phenylketonuria (PKU) and other disorders requires accurate measurement of analytes in blood eluted from filter paper. The development of new quantitative methods for phenylalanine measurement in dried blood spots for PKU screening has introduced an increased number of calibrators provided with the kits. We compared the phenylalanine values of seven different sets of calibrators (six from commercial sources and one from a screening laboratory), all measured with the same technique. METHODS: Two types of filter papers, S&S #903 and S&S #2992 were used. Phenylalanine was measured by high performance liquid chromatography (HPLC). RESULTS: There was a wide variation in the phenylalanine values assigned to the seven different sets of calibrators used, with the ratios of HPLC to assigned value ranging from 0.68-1.62. This could not be only explained by the use of different types of filter papers. However, factors in calibrator preparation did influence the measured concentration. These included higher values when 100 microliters rather than 35 microliters of blood was spotted, when the red blood cells were intact rather than lysed, and as the hematocrit increased. DISCUSSION: These observations emphasize the need to establish recommendations for preparation of dried blood calibrators in order to appropriately compare new techniques and exchange screening experiences among centers.

Calibration↗
PubMed1996

International database of tetrahydrobiopterin deficiencies.

Approximately 2% of newborns with hyperphenylalaninaemia are deficient in tetrahydrobiopterin. Selective screening must be performed in all instances where hyperphenylalaninaemia is detected by neonatal screening. In the last 20 years, 308 patients with tetrahydrobiopterin deficiencies have been recognized as a result of screening carried out, worldwide, in Departments of Paediatrics. Of these 308 patients, 181 suffered from 6-pyruvoyltetrahydropterin synthase deficiency, 92 from dihydropteridine reductase deficiency, 13 from pterin-4a-carbinolamine dehydratase deficiency, 12 from GTP cyclohydrolase I deficiency, and 10 are still unclassified. In the BIODEF database we have tabulated the most common clinical and laboratory data related to hyperphenylalaninaemia and tetrahydrobiopterin deficiencies. Additionally, there are data regarding treatment, outcome, and DNA analysis. Preliminary evaluation reveals that the degree of hyperphenylalaninaemia can vary from normal to 2500 mumol/L. Analyses of pterins in urine and measurement of dihydropteridine reductase activity from Guthrie cards are absolutely essential tests for accurate diagnosis. There is a regional (demographic) variation in the frequency of tetrahydrobiopterin deficiencies indicating the highest incidence in Saudi Arabia, probably a consequence of the high consanguinity rate.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Population-based differences in thyrotropin and thyroxine distributions in healthy newborns revealing results from independent reagent evaluation.

An independent evaluation of reagents for the determination of thyroxine and thyrotropin from dried blood spot samples taken from newborns between the third and fifth day of life revealed striking differences in the thyrotropin distribution among newborns from Byelorussia. An analysis of the thyrotropin distribution from Byelorussian newborns showed that 40% of samples had over 5 mIU/l blood. In other European populations comparable in respect to timing of blood collection, this fraction varied from only 1% (Stockholm, Sweden) to 3.7% (Lille, France). The reason for the "shift right" in Byelorussian newborns remains to be further investigated. This shift can be attributed to the synergetic effects of mild-moderate iodine deficiency and/or as yet unidentified environmental factors. The differences observed in cumulative distribution patterns obtained by two commercial methods question the use of absolute figures (such as the proportion of samples over 5 mIU/l) for the purpose of inter-population comparisons.

France↗
PubMed1995

Changes of cerebral biopterin and biogenic amine metabolism in leukemic children receiving 5 g/m2 intravenous methotrexate.

Acute or subacute neurologic disorders can be observed in patients receiving high-dose methotrexate therapy for lymphoblastic leukemia or malignant tumor. Impairment of biopterin metabolism leading to decreased availability of monoamine neurotransmitters has been suggested to explain methotrexate neurotoxicity. To investigate such a mechanism, we have measured prospectively by HPLC the concentrations of total biopterin, homovanillic acid, and 5-hydroxyindolacetic acid in cerebrospinal fluid of 57 children with acute lymphoblastic leukemia. A sequential analysis of cerebrospinal fluid was performed for each patient: cerebrospinal fluid samples were obtained before therapy and after each of the four high-dose methotrexate infusions during the CNS prophylaxis phase. A significant increase of total biopterin concentrations in cerebrospinal fluid was observed after high-dose methotrexate therapy compared with the pretreatment values. No cumulative effect was noted. In contrast, no significant variation of the homovanillic acid and 5-hydroxyindolacetic acid levels was observed in cerebrospinal fluid. However, individual analysis revealed a transient decrease of homovanillic acid and 5-hydroxyindolacetic acid concentrations in cerebrospinal fluid of six children. The increase of total biopterin mimicking that observed in inherited dihydropteridine reductase deficiencies suggests that methotrexate inhibits the regenerating system of biopterin in the brain of patients undergoing high-dose methotrexate therapy.

Adolescent↗
PubMed1995

[Epidemiological data. Neonatal and prenatal screening].

Unlike what is generally thought, cystic fibrosis is not the most frequent hereditary disease. Its frequency is approximately 1/3 200 and varies with the geographic area. The frequency of heterozygous subjects is about 1/28. No country has established a generalized neonatal screening programme, for technical reasons and because there has been no demonstration of a beneficial effect from early care. It would nevertheless be useful to develop experimental programmes defining which protocols might best be established. Antenatal screening can be based on detecting heterozygous subjects, a technically feasible operation, although answers to a large number of questions would be required.

Cystic Fibrosis↗
PubMed1993

2,4-diamino-7-hydroxy-pteridines in biological fluids of patients on high-dose methotrexate.

Concentrations of 2,4-diamino-7-hydroxy-pteridines in plasma and cerebrospinal fluid (CSF) are reported for the 0.5-8 g/m2 dose range of methotrexate in children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma. This experiment has revealed that: (1) there is a wide inter-individual but relatively narrow intra-individual variability of the maximal concentrations of 2,4-diamino-7-hydroxy-pteridines in plasma during consecutive methotrexate cycles; (2) the increase in the level of the metabolites in plasma was related to increments of the methotrexate dose, but not above 5 g/m2: this can be explained by a saturable conversion of methotrexate to 2,4-diamino-7-hydroxy-pteridines; (3) significant correlations were found between simultaneous values of 2,4-diamino-7-hydroxy-pteridines in plasma and CSF; (4) the formation of 2,4-diamino-7-hydroxy-pteridines did not depend on the ages of patients receiving the same dose of methotrexate. The presence of these compounds in plasma and CSF in significant amounts creates the potential for a number of competitive interactions with pteridine-dependent metabolism which may open up new possibilities for understanding the metabolic side-effects of methotrexate therapy.

Adolescent↗