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OBJECTIVES: Total/near total intestinal aganglionosis (TIA/NTIA) is the most uncommon and life-threatening form of Hirschsprung disease (HD). The management of TIA/NTIA is challenging and the role of autologous intestinal reconstructive (AIR) surgery is controversial. The objective is to evaluate the effectiveness of AIR in patients with TIA/NTIA. METHODS: Records from children affected by TIA and enrolled in the multicenter international Pediatric Intestinal Rehabilitation and Transplantation Registry were retrospectively reviewed. RESULTS: Fourteen patients with TIA were identified. TIA diagnosis was confirmed histologically at the median age of 14 days of life. All received a proximal decompressive jejunostomy. Two patients died, 4 patients had satisfactory stoma output with enteral tolerance without additional procedures, 8 underwent 10 AIR procedures (4 Ziegler myotomy-myectomy, 3 transposition of aganglionic ileum with or without myotomy, 2 simple tapering, 1 longitudinal lengthening and tailoring procedure with associated myotomy). AIR significantly reduced median stoma output, from 197 to 31 mL · kg · day (P = 0.0001). The reduction was seen in all patients. In addition, AIR improved enteral tolerance in the long term in 5 of 8 patients (63%), and temporarily in 1, leading to a reduction of parenteral nutrition requirement from 100% to 70% (P = 0.0231). CONCLUSIONS: AIR surgery in carefully selected patients may be useful and effective way to enhance residual bowel absorptive function and to reduce parenteral nutrition requirements. AIR and intestinal transplantation are complementary surgical tools in the complex treatment algorithm of TIA/NTIA.

Short bowel syndrome (SBS) is the main cause of intestinal failure (IF) in the pediatric population. To promote the standardization of care of these patients, the registry of Pediatric Intestinal Rehabilitation and Transplantation (PIRAT) has been established. The aim of this study is to describe patients with IF using PIRAT database. Data from two tertiary care European referral Centers registered in PIRAT (https://www.studeon.eu/pirat) were analyzed (1994-2015). Neonatal SBS-related IF was defined as need for parenteral nutrition (PN) to sustain life and growth for more than 75 days, after extensive bowel resection during neonatal period. Data included patient demographics, disease at birth, residual small intestine, and intestinal autonomy (PN on/off). In this study, 114 children with SBS-related IF were identified (male 60%). Median gestational age was 35.3 weeks (interquartile range [IQR]: 33.0-38.0); median birth weight was 2,440 g (IQR: 1,700-2,990). The main causes of SBS were intestinal atresia in 31 (27%), midgut volvulus in 29 (25%), necrotizing enterocolitis in 23 (20%), and gastroschisis in 12 (11%). Nine (7.9%) patients died on PN (six sepsis, two IF-associated liver disease, and one multiorgan failure). Median residual small bowel length was 46 cm (IQR: 13.0-92.5). Ileocecal valve was resected in 48 patients (42%). Intestinal autonomy was achieved in 68% patients. We present the web-based registry PIRAT and the first results of patients with IF registered from two European Centers. PIRAT could give the opportunity to create a dedicated international network (IF-net) to standardize, improve, and spread the therapeutic paths for the rare and heterogeneous condition of SBS-related IF.

We report a case of vanishing gastroschisis visualized by antenatal ultrasound with a 7-year long term follow-up. Currently, the child is still dependent on daily parenteral nutrition with no signs of hepatotoxicity. To our knowledge, it's the fourth case with a long-term follow-up. Vanishing gastroschisis is a rare complication of gastroschisis. However, physicians should be aware of it because its prognosis is worse than classical gastroschisis. When a vanishing gastroschisis is visualized or suspected by antenatal ultrasound, prenatal counseling is required with explanations about the risk of short bowel syndrome, the need of parenteral nutrition and related complications (inflammatory colitis, sepsis, liver failure and organ transplant). Mortality rate was initially around 93%, and dropped to 27% after the years 2000 (versus 10% for classical gastroschisis). After birth, all children will require surgery, and sometimes autologous gastro-intestinal reconstruction. Most survivors (68%) could be taken off the TPN. Unfortunately, long-term outcomes for children with vanishing gastroschisis are still missing in current literature.

BACKGROUND AND AIMS: Anastomotic ulceration (AU) is a rare potential life-threatening complication that may occur after intestinal resection. The diagnosis is often delayed after a long-lasting history of refractory anemia. The pathogenesis remains unknown and there are no established therapies. The aim of the study was to analyze the medical history of children with short bowel syndrome (SBS) who were experiencing AU. METHODS: Records of SBS children were retrospectively reviewed. Demographics, baseline characteristics, presentation, diagnosis and treatment of AU cases were analyzed. RESULTS: Eight out of 114 children with SBS were identified as having AU. Mean gestational age was 32.5weeks. Underlying diseases were: 5 necrotising enterocolitis, 2 gastroschisis and 1 multiple intestinal atresia. The mean age at AU diagnosis was 6.5years (diagnosis delay of 35months). All but 2 patients had AU persistency after medical treatment. Endoscopic treatment (2 argon plasma coagulation; 1 platelet-rich fibrin instillation; 2 endoscopic hydrostatic dilations) was effective in 3 out of 5 children. Surgery was required in 3 patients. CONCLUSIONS: Severe bowel ischemic injury, especially in preterm infant, could predispose to AU development. Medical treatment showed discouraging results. We firstly described that different endoscopic treatment could be attempted before resorting to further surgery. LEVEL OF EVIDENCE: IV.

Notre recherche a pour objet l'élaboration et la validation d'un protocole d'évaluation de la sensorialité orale et des conduites alimentaires du jeune enfant destiné aux orthophonistes. Tenant compte des données de la littérature et de l'existant, notre protocole a fait l'objet de pré-tests, d'une validation fonctionnelle par groupes nominaux d'orthophonistes et d'une expérimentation en crèche sur un échantillon de 23 enfants tout-venant de 8 à 18 mois. Les groupes nominaux identifient plusieurs points : l'appropriation aisée de l'outil par les orthophonistes, la conduite d'une évaluation mettant en évidence les difficultés, les comportements émergents et les compétences de l'enfant, l'identification d'items pertinents pour construire les lignes de base de la rééducation. L'expérimentation a permis d'élaborer des normes et de dégager des indicateurs pour les prises en charge, notamment en termes de progression.

"Anastomotic ulcers in short bowel syndrome: looking for the optimal therapy"

Le diagnostic de dénutrition via l'examen clinique des réserves musculaires semble tout à fait indiqué en pédiatrie. La mesure d'accord avec l'évaluation nutritionnelle pédiatrique de référence (SGNA) est élevée (K > 0.6), la sensibilité également (+/- 90%) et la faisabilité jugée importante (médiane 8/10).

Le diagnostic de dénutrition via l'examen clinique des réserves musculaires semble tout à fait indiqué en pédiatrie. La mesure d'accord avec l'évaluation nutritionnelle pédiatrique de référence (SGNA) est élevée (K > 0.6), la sensibilité également (+/- 90%) et la faisabilité jugée importante (médiane 8/10).

L’attachement témoigne pour l’enfant du besoin d’une présence et d’une protection physique et psychique. Il contribue au développement de ses habiletés sociales et affectives. Toutefois, le lien entre l’attachement, la cognition et le développement physique reste à établir. Objectif : Évaluer l’effet de la qualité de l’attachement sur le développement cognitif et physique d’enfants placés en institution pour enfants abandonnés à Kinshasa. Matériel et méthodes : Quatre-vingt-quatre enfants âgés de 4 à 7 ans, dont 42 enfants abandonnés placés en institution résidentielle et 42 enfants vivant en famille ont participé. L’évaluation a porté sur les qualités de l’attachement, les performances cognitives et le développement physiques. Instruments : L’attachment story completion task (ASCT), les matrices de Raven (CPM) et le growth vision ont été utilisés. Le test de t de Student a été utilisé pour la comparaison de la qualité de l’attachement, les performances cognitives et le développement physique des enfants. Résultats : Un attachement sécurisant a été trouvé plus fréquemment parmi les enfants vivants en famille (66,7 %) qu’en institution (33,3 %). Aux matrices de Raven, les enfants vivant en famille ont obtenu une moyenne plus élevée (19,3) que celle des enfants vivant en institution (13,3). De plus, pour les enfants avec attachement sécurisant, la moyenne aux matrices de Raven et le rapport taille pour âge se chiffrait, respectivement à 83,7 % en famille et 73,1 % en institution. Les valeurs moyennes respectives, pour les enfants avec attachement non sécurisant, étaient plus faibles que pour ceux avec attachement sécurisant en famille (80,7 %) et en institution (70,9 %). Toutefois, nonobstant la qualité de l’attachement, les moyennes en famille étaient supérieures à celles observées en institution. Conclusion : Ces résultats suggèrent que le développement de l’enfant, aussi bien cognitif que physique, est tributaire de la qualité de l’attachement. La vie en famille of

L’examen des pertes de masse musculaire et de masse grasse sous-cutanée n’est en général pas pris en compte dans le diagnostic de la dénutrition en pédiatrie, alors qu’il permet d’identifier environ 70% des patients dénutris. Cet examen physique est donc prioritaire et doit être complété au minimum par l’analyse de la croissance staturopondérale. Une démarche diagnostique reprenant les critères par ordre de priorité doit être étudiée.

PURPOSE OF REVIEW: Autologous intestinal reconstructive surgery has evolved over the past 3 decades from rescue to main surgical procedure in the multidisciplinary approach to short bowel syndrome (SBS) patients with intestinal failure. The purpose of this review is to clarify the actual place of intestinal reconstructive surgical techniques in the management of intestinal failure related to SBS and their relationship with intestinal transplantation. RECENT FINDINGS: Recent reports from centers of excellence in intestinal rehabilitation underline the efficacy and safety of autologous intestinal reconstructive surgery in patients with SBS. Outcome parameters as survival, parenteral nutrition weaning, and clinical conditions were improved in SBS patients treated by gastrointestinal reconstructive surgery. SUMMARY: Autologous intestinal reconstructive procedures are pivotal to achieve enteral autonomy in patients with intestinal failure related to SBS. They should be considered mutually supportive and not antagonistic to intestinal transplantation.

The serial transverse enteroplasty (STEP) is a safe and successful procedure to lengthen the small bowel. Several patients develop postoperative bowel redilatation with loss of bowel adaptation. We describe a 2-month-old male infant with short bowel syndrome who developed dilatation of the lengthened segment after STEP, which was successfully treated by a longitudinal intestinal lengthening and tailoring procedure. To the best of our knowledge, this is the first described case of longitudinal intestinal lengthening and tailoring procedure after STEP.

Objective: To explore facilitators and barriers to participation in physical activity and sport in youth with cerebral palsy (CP). Study design: This was a qualitative study involving in-depth focus group interviews with 33 ambulatory youth with CP and their parents. The interviews were conducted until informational redundancy was achieved. Results: Youth with CP and their parents reported personal and environmental facilitators and barriers to participation in physical activity. Seven major themes related to personal and environmental factors were identified. Conclusions: This study suggests that various personal and environmental factors play a key role in determining the extent to which youth with CP participate in physical activity. The facilitators and barriers identified provide important theoretical insights into how and why youth with CP and their parents might change their physical activity behavior. © 2012 Mosby, Inc.

During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Les enfants atteints de maladies chroniques à risque vital demandent une prise en charge spécifique dont la dimension palliative est importante. Ces patients développent une importante morbidité bronchopulmonaire. Leur mortalité est fréquemment attribuée à des causes respiratoires. Ces enfants dont le diagnostic premier n=est pas respiratoire développent progressivement une pathologie respiratoire évolutive, qui comporte souvent des complications infectieuses chroniques, une insuffisance respiratoire chronique, pouvant évoluer vers l=insuffisance respiratoire aigue. De nouvelles technologies respiratoires sont maintenant disponibles : échelles de dyspnée, techniques d=aide à la toux (cough-assist ), à la mobilisation des sécrétions, ventilation non invasive nocturne, ventilation invasive sur trachéotomie avec utilisation de micro L=intégration de ces moyens de diagnostic et de traitement à la prise en charge de la pathologie respiratoire chronique de ces patients soulève des questions d=ordre éthique, concernant l=incertitude du pronostic et du temps qui reste à vivre, l=amélioration de l=espérance de vie due au traitement de l=insuffisance respiratoire, la valeur de quelques mois ou quelques années de vie d=un enfant. Nous observons que les enfants atteints de maladies chroniques à risque vital sont le plus souvent traités lorsqu=ils présentent des épisodes aigus, mais qu=ils ne bénéficient pas de traitement de fond visant à prévenir les récidives infectieuses, à ralentir l=évolution de l=insuffisance respiratoire. La prise en charge palliative de ces enfants, qui se doit d=être la plus précoce possible, devrait intégrer une réflexion stratégique, réfléchie, multidisciplinaire, incluant l=enfant et sa famille, de la pathologie respiratoire chronique dont il est et sera atteint

BACKGROUND: Bacterial infections in infants constitute a risk factor for parenteral nutrition (PN)-related cholestasis. The possible role of infections in the development of liver fibrosis, the most severe long-term complication, has yet to be documented. This study retrospectively compares the incidence of sepsis in children with and without severe liver fibrosis. PATIENTS AND METHODS: Medical reports of 30 children in prolonged PN programs between March 1985 and March 2000 were reviewed. Starting at birth, the mean PN duration was 65 months (range, 8-150 months). According to the results of liver biopsy (LB), patients were split into 2 groups: group A (n = 16) with severe liver fibrosis (ie, septal fibrosis involving >50% of portal fields or cirrhosis) and group B (n = 14) with normal hepatic architecture or mild fibrosis (<50% of portal fields). RESULTS: Duration of PN at the time of LB was shorter in group A (30.5 months; range, 8-96 months) than in group B (105 months; range, 37-150 months; P < 0.001). In group A the incidence of sepsis was significantly higher than in group B (3.2 +/- 0.3/year vs 1.5 +/- 0.2/year) and the first infection occurred earlier (group A, 1 month [range, 1-2 months]; group B, 4 months [range, 1-19 months]). By contrast, both groups were similar in terms of pregnancy duration, birth weight, age of PN onset, underlying diseases, mode of PN delivery, and number of cholestasis episodes. CONCLUSIONS: Incidence and early onset of infections may contribute to the development of liver fibrosis in cases of long-term PN. New strategies are required in prevention and treatment of infections in children receiving PN.

The Paediatric Liver Transplant Program at Saint-Luc University Clinics constitutes a substantial single centre experience, including 667 transplantations performed between March 1984 and April 2003, and the history of this program reflects the tremendous progress in this field since twenty years. Liver transplantation in children constitutes a considerable undertaking and its results depend on multiple, intermingled risk factors. An analysis of the respective impact of several surgical and immunological parameters on patient/graft outcome and allograft rejection after paediatric liver transplantation showed a significant learning curve effect as well as the respective impact of pre-transplant diagnosis on survival and of primary immunosuppression on the rejection incidence. The introduction of living related liver transplantation in 1993 not only permitted to provide access to liver replacement in as many as 74% more candidate recipients, but also resulted in better graft survival and reduced retransplantation rate. The results of a recent pilot study suggest that steroid avoidance is not harmful, and could even be beneficial for paediatric liver recipients, particularly regarding growth, and that combining tacrolimus with basiliximab (anti-CD25 chimeric monoclonal antibody) for steroid substitution appears to constitute a safe alternative in this context. The long-term issues represent the main future challenges in the field, including the possibility of a full rehabilitation through immunosuppression withdrawal and tolerance induction, the development of adolescence transplant medicine, and the risk of early atherogenesis in the adulthood.

Primary duodenogastric reflux is a rare disorder in adults which has not yet been documented in children. Six young patients, aged 4.5 to 16.5 years (median 13.5 years) presented with atypical reflux symptoms persisting from 1 to 84 months (median 8 months) and unresponsive to classical antacid therapy. In all six patients, 24 h gastric bilimetry showed excessive bile exposures for absorbances ranging from 0.25 to 0.60. The fraction of time (supine period) above the 0.25 absorbance threshold ranged from 30% to 75% while the 95th percentile value for healthy adults is 31%. In all patients tested, hepato-iminodiacetic acid scintigraphy revealed the occurrence of a massive duodenogastric reflux and four out of five patients had an alkaline shift (fraction of time pH >8 on 24 h lower oesophageal pH monitoring) ranging from 4.2% to 20% (control values 0.0% to 2.9%). Endoscopic findings included abundant bilious gastric leak (6/6) and chronic prepyloric Helicobacter pylorinegative gastritis (2/6). Daily administration of cisapride, sucralfate with or without omeprazole resulted in an improvement of symptoms in five patients within 15 days. This treatment was ineffective in one patient who became symptom-free only after a surgical duodenal switch with fundoplication was performed. Conclusion: primary duodenogastric reflux is a rare foregut disorder of unknown origin occurring in late childhood. If suspected, 24 h intragastric bilimetry appears to be a useful investigation to confirm the diagnosis.

Nutrition et troubles digestifs de l'enfant

BACKGROUND: The depletion of differential B cell and xenoreactive natural antibodies (XNA) by anti-delta and anti-mu injections was analyzed in adult mice. Sequential treatment with anti-delta and then anti-mu induces a complete depletion of B cells and XNA and represents a potential approach to induce xenograft tolerance. METHODS: Adult mice were injected with anti-mu, anti-delta, anti-delta then anti-mu, or control isotype monoclonal antibodies from day 0 to day 14. The different B-cell populations were analyzed by FACS and immunohistology. Ig production was tested by ELISA. XNA were analyzed by FACS. RESULTS: Anti-mu injections induced a depletion of IgMhigh, immature B cells, marginal zone B cells, and B1 cells and an increase of IgG-XNA production. Anti-delta injections induced mature conventional IgDhigh B-cell depletion and increased IgM-XNA production. Interestingly, sequential injections of anti-delta then anti-mu induced a depletion of immature B cells, mature B cells (MZ, B2, and B1), and XNA. CONCLUSIONS: These results demonstrate that mature B-cell depletion in adult mice can be obtained by mAb injections and depends on the surface immunoglobulin cross-linking threshold. Indeed, anti-mu mAb depleted IgMhigh B cells (MZ and B1) and anti-delta, IgDhigh B cells (B2). The differential B-cell suppression shows that conventional B cells are responsible in the IgG-XNA production and MZ and B1 cells in the IgM-XNA production. Sequential repeated injections of anti-delta then anti-mu mAb depleted all B-cell populations and suppressed the whole XNA production.

BACKGROUND: Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic effects on human and rat small intestinal mucosa. AIMS: To examine the effects of S boulardii on ileal adaptation after proximal enterectomy in rats. METHODS: Wistar rats, aged eight weeks, underwent 60% proximal resection or transection and received by orogastric intubation either 1 mg/g body wt per day lyophilised S boulardii or the vehicle for seven days. The effects on ileal mucosal adaptation were assessed eight days after surgery. RESULTS: Compared with transection, resection resulted in mucosal hyperplasia with significant decreases in the specific and total activities of sucrase, lactase, and maltase. Treatment of resected animals with S boulardii had no effect on mucosal hyperplasia but did upgrade disaccharidase activities to the levels of the transected group. Enzyme stimulation by S boulardii was associated with significant increases in diamine oxidase activity and mucosal polyamine concentrations. Likewise, sodium dependent D-glucose uptake by brush border membrane vesicles, measured as a function of time and glucose concentration in the incubation medium, was significantly (p<0.05) increased by 81% and three times respectively in the resected group treated with S boulardii. In agreement with this, expression of the sodium/glucose cotransporter-1 in brush border membranes of resected rats treated with S boulardii was enhanced twofold compared with resected controls. CONCLUSION: Oral administration of S boulardii soon after proximal enterectomy improves functional adaptation of the remnant ileum.

The mechanism(s) by which rat immature enterocytes exhibit increased responsiveness to insulin before weaning is unknown. Therefore, we have analyzed the distribution, ontogeny, and molecular properties of insulin receptors (IR) and of related substrates in immature and mature enterocytes. IR were studied by radioligand binding assays, cross-linking labeling, immunohistochemistry, and in vitro phosphorylated substrates by immunoprecipitation. Regardless of age, 125I-insulin binding to IR was five times higher in crypt cells than in villus cells and two times higher in the ileum than in the jejunum. Binding capacity to villus cells from sucklings (day 14) exceeded three times that of older animals (day 30 and day 60). Scatchard analysis of equilibrium binding data confirmed an age-related decrease in low- and high-affinity receptor classes without change in affinity constants. In concordance, both alpha- and beta-IR subunits were more abundant in immature than in mature membranes. In vitro, insulin elicited the phosphorylation of three membrane proteins (96, 60 and 42 kDa), whose signals were virtually inhibited by preincubating membranes with antireceptor monoclonal antibodies. By immunoprecipitation, the 60-kDa signal was rapidly detected as a tyrosine-phosphorylated protein, expressed in mature and immature membranes, and identified as a receptor substrate phosphorylated in vitro by the IR tyrosine kinase. In conclusion, 1) increased responsiveness of rat immature enterocytes to insulin could be related to high membrane concentrations of IR and 2) normal rat enterocytes express a 60-kDa phosphotyrosine protein identified as a direct substrate of the IR tyrosine kinase.

Progressive familial intrahepatic cholestasis (PFIC) is a lethal inherited childhood cholestasis of hepatocellular origin. Different subtypes of PFIC have been described according to serum gamma-glutamyl transpeptidase (GGT) activity. There is currently no effective medical therapy available for children with PFIC. We report on 39 patients with PFIC who received ursodeoxycholic acid (UDCA) orally (20-30 mg/kg b.w./day) for a period of 2 to 4 years. Group 1 (n = 26) consisted of children with normal GGT activity, and group 2 (n = 13) of children with high GGT activity. Within group 1, liver tests normalized in 11 children, improved in 5, and stabilized or worsened in 10. Within group 2, liver tests normalized in six children, improved in four, and stabilized or worsened in three. Improvement of parameters was associated with an enrichment of the circulating pool of bile acids with UDCA. Hepatosplenomegaly and pruritus disappeared or diminished in children in whom liver tests normalized. In nine of these children, liver tests worsened and normalized again after stopping and restarting UDCA. Liver histology assessed in four children after normalization of liver tests and 2 years of treatment showed a decrease in fibrosis. We conclude that UDCA should be considered in the initial therapeutic management of children with PFIC, because it appears effective in resolving or improving the liver function and the clinical status of a fair proportion of children. Chronic UDCA therapy might thus avoid the need for liver transplantation in some children with PFIC.

Hyperbilirubinemia in Crigler-Najjar disease type I (CN) can be partially controlled by daily phototherapy, but these children remain at permanent risk of developing brain damage due to kernicterus. Because liver transplantation is the only available curative treatment for liver-based inborn errors of metabolism, orthotopic liver transplantation (OLT) was performed in six patients with CN. Mean age at surgery was 52.5 months (range 27 to 100). Despite a mean daily phototherapy of 12.4 +/- 0.8 hr, mean bilirubin of the 6 patients was 388 microM/L (range 175 to 703) before OLT; one of them was also being treated with tin-protoporphyrin. All 6 had elevated AST/ALT, ranging from 1.4 to 6 times upper normal values. Complications occurred in three patients after OLT, including miliary tuberculosis in one, graft rejection and retransplantation in one, and hepatic artery thrombosis in one. All patients survive with normal serum bilirubin level (follow up 6 to 116 months). Four have normal enzymes on post-OLT follow-up (30 to 95 months), follow a normal education program, and have a normal social life. One recently transplanted patient has progressively normalizing liver function tests 6 months after OLT. One patient transplanted at 8 y.o. (now 116 months post-OLT) has moderate neurological delay due to pretransplant kernicterus, and posttransplant chronic persistent hepatitis. Our series shows that OLT cures hyperbilirubinemia in CN patients, with an excellent survival prospect. The procedure should be decided upon before neurological sequelae occur, since these persist after transplantation.

Two siblings presented with neonatal cholestasis and early liver insufficiency. The older was admitted for end-stage cirrhosis with severe hypoglycemia and had long-term successful liver transplant at the age of 15 months. The second child presented a similar neonatal history of cholestasis, hypoglycemia, hyperlactacidemia, liver insufficiency and progressive cirrhosis. Extensive work-up excluded all known causes of neonatal cholestasis. Gluconeogenesis was found normal following alanine and fructose infusion. Repeated hypoglycemia with early post-prandial hyperlactacidemia led us to investigate the mitochondrial respiratory chain enzyme activities. Selective defects of complexes I, III and IV, coded by mitochondrial DNA, were detected in liver tissue of this patient and on preserved frozen tissue from his sibling, whilst normal activities were found in liver tissue samples from control patients with end-stage liver diseases. No extrahepatic manifestations were found. We conclude that liver deficiency of mitochondrial respiratory chain enzymes may cause liver disease in neonates, associated with hypoglycemia and post-prandial hyperlactacidemia. The disease is cured by liver transplantation.

From a study of the collision-activated fragmentation of bile acids, a qualitative analytical method based on negative ion fast atom bombardment tandem mass spectrometry has been developed. The times for sample preparation and analyses are short. Both free and conjugated bile acids are detected as they occur in biological fluids, without derivatization. For identifying bile acids and conjugates, the method offers better specificity and sensitivity than does the fast atom bombardment mass spectrometric technique alone. Specific scan modes have been developed for the selective detection of taurine conjugates, delta 4-unsaturated taurine conjugates, delta 4-3-keto free acids and their glycine conjugates, free acids and glycine conjugates bearing a hydroxyl group at the C-12 position, sulfates of glycine and taurine conjugates, and a C29 dicarboxylic bile acid, specific for generalized peroxisomal disorders. Applications of this technique demonstrate its potential usefulness, principally in the diagnosis of several peroxisomal disorders.

From a study of the collision-activated fragmentation of bile acids, a qualitative analytical method based on negative ion fast atom bombardment tandem mass spectrometry has been developed. The times for sample preparation and analyses are short. Both free and conjugated bile acids are detected as they occur in biological fluids, without derivatization. For identifying bile acids and conjugates, the method offers better specificity and sensitivity than does the fast atom bombardment mass spectrometric technique alone. Specific scan modes have been developed for the selective detection of taurine conjugates, DELTA-4-unsaturated taurine conjugates, DELTA-4-3-keto free acids and their glycine conjugates, free acids and glycine conjugates bearing a hydroxyl group at the C-12 position, sulfates of glycine and taurine conjugates, and a C29 dicarboxylic bile acid, specific for generalized peroxisomal disorders. Applications of this technique demonstrate its potential usefulness, principally in the diagnosis of several peroxisomal disorders.