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The main nonconformities enumerated to facilitate consensual codification. In each case, an action is defined: refusal to realize the examination with request of a new sample, request of information or correction, results cancellation, nurse or physician information. A traceability of the curative, corrective and preventive actions is needed. Then, methodology and indicators are proposed to assess nonconformity and to follow the quality improvements. The laboratory information system can be used instead of dedicated software. Tools for the follow-up of nonconformities scores are proposed. Finally, we propose an organization and some tools allowing the management and control of the nonconformities occurring during the pre-examination phase.

Resume Un programme experimental de detection neonatale de la drepanocytose a ete initie en France metropolitaire en 1990. Apres les depistages mis en place en Guadeloupe et Martinique et differentes experiences regionales, sa strategie a ete affinee. Depuis le debut de 1994, ce depistage est integre dans trois regions a celui de la phenylcetonarie, de l'hypothyroldie et de l'hyperplasie congenitale des surenales mais n'interesse que les enfant ⪡a risque⪢, aelectionnes par les maenites en fonction de l'origine ethnique des parents. Ce depistage peul etre realire a un cout acceptable, par des methodes fiables, me generant que tres peu de faux positifs et de faux negatifs. Les conditions de prise en charge des enfants depistes ont ete definies. Tous les enfants depistes jusqu'ici sont effectivement salvis et se developpent normalement. La generalisation du depistage a l'ensemble de la France, eavisagee pour la fin du siecle, necessitera de gros efforts d'information et une grande vigilance

The principle of pilot or evaluative studies has been adopted by the French Association for Neonatal Screening to investigate all the components of a new screening action before it is proposed as an addition to the ongoing program. Such studies have recently been undertaken to evaluate the feasibility of the screening for cystic fibrosis, congenital adrenal hyperplasia and sickle cell disease on a national basis. The conclusions of the respective analyses were: (i) To not recommend cystic fibrosis screening with a ‘two-step’ strategy using the immunoreactive trypsin measurement for both the primary screen and the repeat blood testing, because of the high recall rate (1.9%) and the risk of false negatives (7.4%). (ii) To improve the strategy of congenital adrenal hyperplasia screening before nation-wide screening in order to reduce the number of false positives, especially in premature babies. (iii) To propose screening for sickle cell disease in areas that include a high percentage of the ‘at-risk’ population.

We have evaluated the Quantase™ Phenylalanine Kit for the determination of phenylalanine in dried blood samples taken in the neonatal period for phenylketonuria (PKU) screening. The assay is linear to blood phenylalanine concentrations of at least 20 mg/dl (1.2 mmol/1). Coefficients of variation of about 5% for both within- and between-run was observed around the cut-off level (3–4 mg/dl). Easy automation enables the handling of large numbers of samples for screening and quantitative measurements.

The French Association for Neonatal Screening was created in 1975 in response to the need for an organization to coordinate neonatal screening activities in France. The program of ‘systematic’ neonatal screening has been voluntarily limited to the screening of phenylketonuria and congenital hypothyroidism, and is based on regional delegations. Although screening has not been legally mandated, the percentage of coverage has been very high (99.7%), with 17 million newborns screened for phenylketonuria and 10 million screened for congenital hypothyroidism. The organization also includes regional centralization for follow-up which provides data for evaluation of all aspects of the program.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase. To date, more than 530 mutations in the PAH gene have been reported. In Tunisia, this disease seems to be the result of point mutations, few studies have been published about molecular defects of PKU in our country. In this study, we report a novel deletion in exon 6 of two brothers in a Tunisian family after DHPLC analysis and sequencing of the exon 6 of the PAH gene.

Resume Les formes symptomatiques d'hyperphenylalaninemie sont devenues rares en France depuis l'instauration du depistage neonatal systematique. Observation Un enfant ne en Algerie de parents consanguins a ete vu a l'âge de 2 ans pour le bilan d'une encephalopathie convulsivante severe avec hypotonie. La Chromatographie des acides amines a revele une hyperphenylalaninemie ; celle-ci etait liee a un deficit en dihydropteridine reductase. Le regime pauvre en phenylalanine et l'administration de precurseurs des neurotransmetteurs, L-dopa et 5-hydroxytryptophane, n'ont que peu ameliore l'epilepsie et le retard psychomoteur de l'enfant. Commentaires Le diagnostic d'hyperphenylalaninemie doit etre evoque devant une encephalopathie progressive de la premiere annee de vie survenant chez un enfant ne dans un pays ou le depistage neonatal n'existe pas.

Introduction . Sensitive screening for phenylketonuria (PKU) and other disorders requires accurate measurement of analytes in blood eluted from filier 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 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 μl rather than 35 μl 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.

Mannose-rich oligosaccharides have been isolated from urines of 5 patients with mannosidosis. Their compositon and structure were determined. Three of them have been previously described by Norden et al: alpha p-Manp-(1 leads to 3) beta-d-Manp-(1 leads to 4) d-GlcNAcp; alpha-p-Manp-(1 leads to 2), alpha-d-Manp-(1 leads to 3) beta-d-Manp-(1 leads to 4) d-GlcNAc and alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 3) beta-d-Manp-(1 leads to 4) d-GlcNAcp, but the four others are new entities: alpha-d-Manp-(1 leads to 3) (alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 6) beta-d-Manp-(1 leads to 4) GlcNAcp; alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 3) (alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 6) beta-d-Manp-(1 leads to 4) GlcNAcp; alpha-d-Manp-(1 leads to 2), alpha-d-Man-(1 leads to 3) (alpha-d-Manp-(1 leads to 6) beta-d-Manp-(1 leads to 4) GlcNAp and alpha-d-Manp-(1 leads to 2) alpha-d-Manp-(1 leads to 3) (alpha-d-Manp-(1 leads to 6) beta-d-Manp-(1 leads to 4) GlcNAcp. These structures are related to the glycans of "oligomannosidic type" present in numerous glycoproteins. All possess a N-acetylglucosamine residue in terminal reducing position and reinforce the hypothesis of Kobata et al. and Montreuil et al. that catabolism of glycans N-glucosidically linked to the protein moiety begins by the aciton of a beta-endo-N-acetylglucosaminidase.

Resume Maladie frequente et grave de l'enfant, la mucoviscidose (CF) a deja suscite de nombreuses tentatives de depistage systematique, mais la fiabilite discutable des tests proposes n'avait pas permis d'en generaliser l'application. Le dosage de la trypsine immunoreactive dans un eluat de sang seche est, en revanche, un marqueur fiable et les etudes preliminaires portant actuellement dans le monde sur quelques 3 millions de tests ont donne des resultats interessants. Dans notre travail nous analysons les 3 aspects de ce depistage : dosage de la TIR, resultats et organigramme de depistage. La trousse de dosage utilisee (RIA Gnost trypsine neonatal de Behring) obeit a une methodologie RIA compatible avec le depistage; les coefficients de variations intra- et interessais sont de 2 a 6% et de 4 a 15% pour des valeurs de TIR entre 100 et 1 800 ng/ml; la limite de detection est de 100 ng/ml; l'utilisation d'une pastille de d=4,25 mm permet de reduire au minimum les prelevements insuffisants. Un histogramme des valeurs sur 5 000 nouveau-nes donne une valeur moyenne a 200 ng alors que les malades ont un taux habituellement superieur a 900 ng/ml. Les resultats «suspects (>700) comprennent de nombreux faux-positifs avec une majorite de formes transitoires habituellement liees a une pathologie neonatale intercurrente (detresse respiratoire avec anoxie, infection, anomalie chromosomique, insuffisance renale…). La valeur predictive positive de ce resultat anormal n'etant que de 5%, il est propose une strategie en deux temps ou tout resultat anormal fait l'objet d'un controle sur un deuxieme prelevement ce qui permet d'eliminer les formes transitoires et eleve la valeur predictive positive du deuxieme resultat a 75%. Les faux negatifs sont possibles surtout en cas d'ileus meconial mais aussi dans des formes habituelles de CF sans qu'il y ait d'explication a ces resultats «normaux. En conclusion, le dosage de TIR sur sang seche permet le depistage neonatal de la CF; la strategie en 2 temps augmente la specificite du test. Si l'on tient compte qu'une prise en charge precoce (avant la 5e semaine de vie) ameliore la qualite de vie du malade, et augmente peut-etre son esperance de vie, que le cout du depistage est facilement compense par la reduction aujourd'hui demontree de la morbidite et que les parents sont favorables a ce depistage, il est evident que les conditions sont realisees pour proposer une telle action qui aura par ailleurs l'avantage, par le reperage precoce des familles a risque, d'eviter la recidive en leur proposant en cas de grossesse un diagnostic prenatal aujourd'hui accessible (biologie moleculaire ou dosage des enzymes intestinales dans le liquide amniotique).

Resume L'auteur realise un survol utile des problemes poses par l'informatique au biologiste : architecture, taches et materiel (micro-ordinateurs, logiciels, peripheriques). L'article constitue une photographie de la situation actuelle de l'utilisation de la micro-informatique : gestion de dossiers (20 % des fonctions assurees), gestion des analyses et controle de qualite (20 %), travaux scientifiques (15 %), fraitement de textes (25 %), tâches de conception (20 %).