[Organization of collaborative deliberation for limiting or withholding treatments in children]. / Comment organiser la délibération collégiale pour limiter ou arrêter les traitements en pédiatrie?

In 2005, the French law on patients' rights at the end of life required that decisions to withdraw or withhold life-sustaining treatments be made and carried out by the physician in charge of the patient, after obtaining advice from an independent consulting colleague and the caregiving team. The purpose of this study was to identify theoretical and practical obstacles to this collaborative deliberation and to propose practical guidelines to organize it.

[The consulting physician for withdrawal of life-sustaining treatments in children]. / Le médecin consultant pour les limitations et les arrêts de traitement en pédiatrie.

In 2005, the French law on patients' rights at the end of life ratified that decisions to withdraw or withhold life-sustaining treatments must be made and carried out by the physician in charge of the patient, after obtaining the advice of an independent consulting colleague. The purpose of this text is to put forward the perspective of a pediatric multidisciplinary workshop regarding the role of the consulting physician and to propose guidelines to help choose this consultant.

Secondary creatine deficiency in ornithine delta-aminotransferase deficiency.

AIMS: Ornithine delta-aminotransferase (OAT) deficiency causes gyrate atrophy (GA) of the retina, as a consequence of high plasma ornithine concentrations. Because creatine synthesis requires the conversion of arginine and glycine into ornithine and guanidinoacetate, high ornithine concentration inhibits this reaction thus causing secondary creatine deficiency. The aim of this study was to evaluate the neuropsychological features and creatine metabolism in patients with GA. METHODS: The study involved 7 GA patients, aged from 11 to 27 years who underwent neuropsychological evaluation and cerebral proton magnetic resonance spectroscopy (MRS). RESULTS: Neurocognitive impairment was found in 5/7 patients, including mental retardation (3/7), school failure (1/7), major visuospatial dyspraxia (1/7), aggressive behavior (3/7) and epilepsy (2/7). Two patients had normal neuropsychological evaluation. Cerebral proton magnetic resonance spectroscopy revealed a profound creatine deficiency in all patients. MRS data were confirmed by decreased levels of creatine and/or guanidinoacetate in plasma and urine in all patients. CONCLUSIONS: In our group of patients with GA, we found a high prevalence of neurological impairment, not reported so far, and possibly related to secondary creatine deficiency and hyperornithinemia. We propose to treat mentally retarded GA patients with high doses of creatine, as it may normalize brain creatine levels and help to reduce ornithine levels.

[D-lactic acidosis in a child with short bowel syndrome]. / Acidose d-lactique chez un enfant présentant un syndrome de grêle court.

INTRODUCTION: d-lactic acidosis is a rare and severe complication of short bowel syndrome in children that may result from important ileal bacterial overgrowth by lactobacilli. Intestinal flora (Lactobacilli) is responsible for the production of d-lactic acid after fermentation of food carbohydrates. OBSERVATION: We report on the case of a 6-year-old child with a short bowel syndrome treated with both home enteral and parenteral nutrition. The patient suddenly presented with acute neurological symptoms including dysarthria and disorientation. Biological analysis revealed metabolic acidosis, increased plasma d-lactic acid assessed by organic acid chromatography analysis and a very important increase in expired hydrogen during glucose breath test. Lactobacillus fermentum (known to produce d and L isomers of lactic acid) was isolated in the gastric liquid and rectal swabs. Clinical and biological evolution was rapidly favourable after treatment with intravenous sodium bicarbonate, antibiotic therapy and interruption of enteral nutrition. CONCLUSION: d-lactic acidosis should be suspected when neurological symptoms occur in a child with short bowel syndrome. They can be prevented by treating intestinal bacterial overgrowth.

Development of liver disease despite mannose treatment in two patients with CDG-Ib.

We report here the 6- and 2-year follow-up of two patients diagnosed at 2 months of age with CDG-Ib who were treated with mannose, with digestive symptoms, liver involvement and hyperinsulinemic hypoglycaemia. Both developed liver fibrosis while general condition improved and other symptoms disappeared.

Methylmalonic and propionic acidurias: management without or with a few supplements of specific amino acid mixture.

In a series of 137 patients with methylmalonic acidaemia (MMA) and propionic acidaemia (PA) diagnosed since the early 1970s, we report in more detail 81 patients (51 MMA and 30 PA) diagnosed between 1988 and 2005. In this series, 14% of patients died at initial access revealing the disease before or despite treatment, 18% died later, and the remainder (68%) are still alive. All patients were treated with the same protocol of enteral feeds with a low-protein diet adjusted to individual tolerance, carnitine, antibiotics, and only occasional use of an amino acid (AA) mixture. There was intensive follow-up and monitoring using measurements of urinary urea. Thirty-nine patients with severe forms, followed for more than 3 years, are analysed in particular detail. Of the 17 PA patients, 6 had moderate disability (all neonatal-onset forms), whereas 11 were normal or slightly delayed in their mental development. Four presented with cardiomyopathy, of whom 2 died. Of the 22 MMA patients, 13 presented in the neonatal period, of whom 3 died later, 2 are in renal failure and only 5 are still alive and have a normal or slightly delayed mental development. In the 9 patients with late-onset forms, there were no deaths and all patients but one have normal mental development. Among the 39 patients, only 40% were given an AA supplement at 3 years, and 50% between 6 and 11 years. The actual intake of natural protein was 0.92, 0.78 and 0.77 g/kg per day at 3, 6 and 11 years, respectively, in patients without AA supplementation, whereas it was 0.75, 0.74 and 0.54 g/kg per day in the group who received small quantities of AA (0.4-0.6 g/kg per day). In both groups, feeding disorders were frequent: 55% at 3 years, 35% at 6 years and 12% at 11 years. Many patients were given a food supplement by tube overnight or were even exclusively tube fed: 60% at 3 years, 48% at 6 years and still 27% at 11 years. Growth velocity was near the normal values. Plasma valine and isoleucine were low to very low, as were leucine and phenylalanine but to a lesser extent. Albumin, vitamins, trace elements and markers of bone metabolism were within the normal values. IGF1, 24-hour urine calcium and body mass density were low. Body composition showed a normal to low lean mass and a normal to high fat mass.

[Neonatal epilepsy and inborn errors of metabolism]. / Epilepsies néonatales et erreurs innées du métabolisme.

Metabolic disorders constitute an important cause of neurologic disease, including neonatal epilepsy. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as hypotonia and/or vigilance disturbances. In most cases, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and electrographic features that are difficult to classify into precise epileptic syndromes. However, specific types of seizures, such as myoclonic seizures or distinctive electroencephalographic patterns, such as suppression burst patterns, epileptic syndrome or early myoclonic encephalopathy, may suggest a specific metabolic disease. The aim of this article is to help clinicians in reviewing potential metabolic diagnoses and approaching metabolic evaluations.

[Malnutrition screening in hospitalized children: influence of the hospital unit on its management]. / Dépistage de la malnutrition chez l'enfant hospitalisé: influence de la structure d'accueil dans la prise en charge.

OBJECTIVES: The aims of this study were to assess the prevalence of malnutrition in a pediatric population hospitalized in a French regional hospital and to evaluate the influence of type of hospital unit (pediatric or not) in the screening and the management of malnutrition. PATIENTS AND METHODS: This one-day cross-sectional survey was performed in three different seasons during 2003. Every child aged 2 months to 16 years old, hospitalized for more than 48 hours was included. Weight for height, Z-score and Body Mass Index Z-score were used for nutritional assessment. Type of hospitalisation unit, date of admission, associated diagnosis, screening and treatment of malnutrition were also taken into account. RESULTS: Two hundred and eighty hospitalized children were undernourished (11%) and thirty-one children were obese (11%) with no difference in prevalence of malnutrition between pediatric and non-pediatric units. At the time of the study, malnutrition was recognized in one third of the children, at a similar rate whatever the type of hospitalized unit. The children hospitalized in pediatrics wards benefited more frequently from nutritional intervention, i.e. dietician care (43 vs. 16% P < 0.01). CONCLUSION: Prevalence of malnutrition in hospitalized children is low and the same in pediatric or non-pediatric units. Screening of malnutrition remains unsatisfactory in hospital. However, malnutrition is more frequently treated in pediatric unit compared with non-pediatric unit.

Renal function outcome in pediatric liver transplant recipients.

The orthotopic liver transplantation (OLT) allows survival of children followed for severe hepatic injury, provided that the immunosuppressive treatment is prolonged. The nephrotoxicity of cyclosporine predicts the long-term outcome of the adult patients receiving a liver transplant. The aim of this study was to determine the long-term outcome of renal function in children receiving OLT. This study included 12 children, with a median for age of 7.1 yr (2-15 yr) at the time of OLT. The duration of follow-up was at least 4 yr, being 7 yr in 10 patients and more than 10 yr in seven. Renal function was evaluated with the serum level of creatinine, calculated glomerular filtration rate (cGFR), and measurement of glomerular filtration rate using chrome 51 ethylenediaminetetraacetate ((51)Cr EDTA) clearance performed at least once during follow-up. The doses and the serum concentrations (C(0)) of cyclosporine were reported at each study time. The cGFR decreased significantly 2 yr after the OLT [median (range): 106 mL/min/1.73 m(2) (71-150) at the time of OLT vs. 85 mL/min/1.73 m(2) (57-128) 2 yr after the OLT, p = 0.03], and decreased again between 7 and 10 yr after OLT [median (range): 99 mL/min/1.73 m(2) (76-125) 7 yr after OLT vs. 81 mL/min/1.73 m(2) (66-140) 10 yr after OLT, p = 0.04]. Six patients developed chronic renal failure (cGFR from 57 to 80 mL/min/1.73 m(2)) 2 yr after OLT associated with high doses of cyclosporine [median (range): 8.8 mg/kg/day (3.5-13)]. The cGFR overestimated renal function by 16% compared with the isotopic measurement of GFR (p = 0.03). Using the (51)Cr EDTA measurement, six of seven patients followed up more than 10 yr after OLT presented mild (n = 3) or moderate (n = 3) chronic renal failure. In our study, the majority of OLT recipients developed a chronic renal failure 10 yr after transplantation. Cyclosporine seems to be the most important factor responsible for the impairment of renal function. The use of the mycophenolate mofetil, a new immunosuppressive agent, allowing a reduction in the dose of cyclosporine, could minimize renal dysfunction. While awaiting the results of a prospective long-term study, close drug monitoring is advised.

[Extensive Hirschsprung's disease associated with intestinal malrotation]. / Maladie de Hirschsprung à forme iléocolique associée à une malrotation intestinale.

Hirschsprung's disease (HD) involves the entire colon in less than 5% of cases, and the association of extensive HD with intestinal malrotation is very rare. This association of symptoms may delay both diagnosis and treatment. An infant presented with an intermittent occlusive syndrome that began neonatally. Intestinal malrotation was diagnosed radiologically, and treated surgically when the child was 2 months old. However, a chronic occlusion persisted. Biopsies of the rectum and the appendix demonstrated an absence of neurons in intestinal plexi. When the child was 17 months old, ileostomy and surgical excision of the segment affected by HD (the colon and terminal ileum) were performed. An ileoanal anastomosis was performed at the age of 29 months, with favorable outcome. The persistence of symptoms of intestinal occlusion after attempted treatment of intestinal malrotation must therefore suggest the possibility of associated HD in a young child.

Congenital idiopathic intestinal pseudo-obstruction and hydrocephalus with stenosis of the aqueduct of sylvius.

We present the first report of an association between hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) and a specific form of congenital idiopathic intestinal pseudo-obstruction (CIIP) in an infant. Diagnosis of HSAS was suspected during the neonatal period because of a severely dilated ventricular system associated with bilateral adducted thumbs, and was confirmed by demonstration of a mutation in the gene encoding L1 cell adhesion molecule (L1CAM). L1CAM mutations cause a variable clinical spectrum. This gene is located at Xq28 and encodes a transmembrane glycoprotein involved in neurite outgrowth and neuronal migration. Hirschprung disease has been reported to involve an L1CAM mutation that manifests as a quantitative defect in the migration of neural crest cells in distal segments of the gut. We report an association that suggests that alterations of L1CAM may cause another type of intestinal pseudo-obstruction distension with a qualitative defect in differentiated Cajal's cells in the anterior part of the gut. This observation suggests that L1CAM has a role in the developmental regulation of multiple systems. Further clinical descriptions of gastroenterological and neuropathological data are required to extend our understanding of the mechanisms underlying L1CAM functions.

Persistence of gastrocutaneous fistula after removal of gastrostomy tubes in children: prevalence and associated factors.

BACKGROUND AND STUDY AIMS: The aims of this study were to determine the prevalence of gastrocutaneous fistula after removal of gastrostomy tubes in children and to identify associated risk factors. PATIENTS AND METHODS: The records of children who had undergone removal of gastrostomy tubes between January 1992 and December 2002 were reviewed retrospectively. Persistent gastrocutaneous fistula was defined as the absence of closure of the gastrostomy 1 month after tube removal. Factors that might influence spontaneous closure of the gastrostomy were studied, including age, underlying disease, nutritional status, type of gastrostomy, replacement of the gastrostomy tube by a button, abdominal wall thickness, duration of gastrostomy tube or button placement, and complications related to the presence of the gastrostomy (infection, granulation tissue). RESULTS: A total of 44 patients were included in the study (mean age 20 months, range 1 day to 14 years). Of these, 28 had undergone percutaneous endoscopic gastrostomy and 16 surgical gastrostomy. The mean time to spontaneous closure was 6 +/- 7 days. Persistent gastrocutaneous fistula developed in 11 patients (25 %) and in seven of these patients this required surgical closure (16 %). The mean duration of gastrostomy placement was significantly longer in patients who went on to develop a gastrocutaneous fistula than in patients who did not develop a fistula (39 +/- 19 months vs. 22 +/- 23 months, respectively, P < 0.03). No other significant association was found between the time required for spontaneous closure and the characteristics of patients or the type of gastrostomy. CONCLUSIONS: Persistent gastrocutaneous fistula is common after removal of gastrostomy tubes in children. Surgical closure should be considered when a gastrostomy has not closed spontaneously 1 month after removal of the gastrostomy tube.

Tolerance and efficacy of intravenous iron saccharate for iron deficiency anemia in children and adolescents receiving long-term parenteral nutrition.

UNLABELLED: The aim of this study was to evaluate the safety and efficacy of intravenous iron saccharate administration in iron-deficient anemic children, under long-term parenteral nutrition, who are unable to tolerate oral iron supplementation or are unresponsive to oral supplementation because of gastrointestinal dysfunction or iron malabsorption. METHODS: Twenty-two infants and children aged 5 months-17 years (median: 38 months) receiving long-term parenteral nutrition and presenting with iron deficiency anemia were included. Total iron to be infused was determined by the formula: total iron (mg) = 0.6 x W (100 - Hb x 100/12) (W: weight, Hb: hemoglobin). Intravenous iron saccharate was given at the hospital. Each patient received a test dose of 25 mg of iron saccharate prior to the initiation of the infusion. Hemoglobin values, reticulocytes count, serum iron, and serum ferritin were determined before iron administration (day 1), as well as 15 and 45 days after iron administration. RESULTS: Tolerance of intravenous iron saccharate was good except in one patient who developed transient exanthema and hypotension after completion of the last iron saccharate infusion. Intravenous iron led to a significative increase in hemoglobin concentration of 2.2 g/dl within 45 days (range: 0.4-4.3 g/dl). CONCLUSION: Intravenous iron supplementation with iron saccharate is an efficient procedure, replenishing iron body stores and significantly increasing the hemoglobin concentration. The possible occurrence of allergic reactions emphasizes the need for close medical supervision.

Neonatal severe intractable diarrhoea as the presenting manifestation of an unclassified congenital disorder of glycosylation (CDG-x).

A case of severe and protracted diarrhoea is reported, which started in the neonatal period and progressively associated with neurological impairment, dysmorphy, hepatosplenomegaly, and hepatic insufficiency, from which the patient died at 2 years of age. Isoelectric focusing of serum transferrin showed a congenital disorder of glycosylation type I pattern but the basic defect could not be identified. This observation shows that congenital disorder of glycosylation is a cause of intractable diarrhoea in neonates.

Characteristics and prevalence of Helicobacter heilmannii infection in children undergoing upper gastrointestinal endoscopy.

BACKGROUND: Helicobacter heilmannii, described in 1983 as a new cause of chronic gastritis, has been reported rarely in children. The purpose of this study was to determine the clinical characteristics and the prevalence of H. heilmannii infection, in comparison with Helicobacter pylori infection in children undergoing upper digestive endoscopy. METHODS: Diagnosis of H. heilmannii was based on its morphologic characteristics in gastric biopsy specimens (two from the antrum, one from the fundus), whereas H. pylori infection was defined by histology and/or culture (one specimen from the antrum, one from the fundus). Respective prevalences of H. heilmannii and H. pylori were calculated in 518 patients studied prospectively who underwent systematic biopsies. RESULTS: The prevalence of H. pylori was 8.9% (46/518) and increased with age (from 2% before 3 years of age to 18% after 10 years). On the contrary, the prevalence of H. heilmannii infection was low, 0.4% (2/518), and no different from that published in adults. After completion of the study period, a third H. heilmannii-infected child was diagnosed. Characteristics of H. heilmannii infection could be studied in these three children 5, 9, and 14 years old. Two of three had abdominal pain and one had dysphagia. Nodular gastritis was observed at endoscopy in two children. H. heilmannii chronic active gastritis (n = 3) was localized in the antrum, associated with an interstitial infiltrate, and could not be distinguished from H. pylori gastritis (n = 46). CONCLUSION: Clinical characteristics, endoscopic features and gastric histopathology did not allow H. heilmannii to be distinguished from H. pylori gastritis in our pediatric population. H. heilmannii infection should be considered and carefully looked for during histologic examination of gastric specimens in cases of H. pylori-negative gastritis.