Estimating the prevalence of congenital disaccharidase deficiencies using allele frequencies from gnomAD.

BACKGROUND: There are currently three known congenital disaccharidase deficiencies: congenital lactase deficiency (CLD), congenital sucrase-isomaltase deficiency (CSD), and congenital trehalase deficiency (CTD). No congenital deficiency has been described for maltase-glucoamylase (MGAM). METHODS: A literature search was performed in PubMed for the pathogenic variants CLD, CSD, and CTD and the articles retrieved were analyzed to estimate the prevalence of congenital disaccharidase deficiencies. RESULTS: Based on reported variants, the estimated prevalence was 1.3 per 106 births (95% CI: 1.1-1.7) for CLD, and 31.4 per 106 births (95% CI: 28.3-34.8) for CSD. Using data on previously reported variants and variants predicted to be loss-of-function in gnomAD, the overall estimated prevalence was 2.3 per 106 births (95% CI: 1.9-2.9) for CLD, 57.6 per 106 births (95% CI:52.5-63.2) for CSD, and 9.2 per 106 births (95% CI: 2.5-3.7) for CTD. CONCLUSION: The prevalence of CSD was found to be relatively high, while for other congenital disaccharidase deficiencies, the estimated prevalence was very low.

MICI-MINOTS: Linguistic and metric validation of a pediatric questionnaire on knowledge about inflammatory bowel disease.

BACKGROUND: Therapeutic education is an essential part of the treatment of chronic diseases, such as inflammatory bowel disease (IBD). The IBD-KID, developed in Canada in English, assesses children's and adolescents' acquired knowledge about their condition and has been validated in Canadian and Australian populations. However, there is no pediatric questionnaire in French to assess patients' knowledge about IBD. OBJECTIVE: To report the linguistic validation process and metric validity of the MICI-MINOTS, the French version of the IBD-KID. METHOD: The translation process consisted of three consecutive steps: forward-backward translation, acceptability testing, and cognitive interviews. The IBD-KID consists of 23 questions, but a 24th question about immunomodulatory therapy was added in the MICI-MINOTS. Psychometric testing was conducted with five groups: children with IBD, their parents, children in a control group, their parents, and health workers recruited from the Timone Pediatric Hospital and the Saint-Sébastien Maternal and Child Protection Center, Marseille, France. A total of 15 individuals completed the tool twice, with a 15-day interval. Internal consistency, reliability, external validity, reproducibility, and sensitivity to change were tested. RESULTS: A total of 38 children with IBD (sex: 20 boys, 18 girls; age: 13.90 [±2.88] years; 25 with Crohn's disease), 20 children in the control group, 58 parents (every child was included with one parent), and 62 health workers were included in the analysis. Intraclass correlation was 0.94 (95% confidence interval 0.83-0.98) for test-retest assessment. Readability using the Scolarius score corresponded to elementary school level. Among the children with IBD, 89.5% answered all 24 questions. For 23 questions, the mean score of children with IBD was higher than among children in the control group: 9.58 (±3.01) versus 5.47 (±3.56), respectively (P<0.01). Parents of children with IBD scored higher than parents of children in the control group: 10.63 (±3.16) versus 8.4 (±3.07), respectively (P=0.012). In the health workers' group, pediatric residents (17.82±3.46) scored higher than nurses 11.75 (±3.4) and ward clerks (8.67±2.40; P<0.01). Patients' knowledge score was significantly related to their parents' knowledge score (r=0.402, P=0.012) for 23 questions. CONCLUSION: The French version of the IBD-KID showed satisfactory psychometric properties to assess knowledge about the disease in French-speaking children.

Mutations in NBAS and SCYL1, genetic causes of recurrent liver failure in children: Three case reports and a literature review.

Acute liver failure (ALF) in childhood is a life-threatening emergency. ALF is often caused by drug toxicity, autoimmune hepatitis, inherited metabolic diseases, and infections. However, despite thorough investigations, a cause cannot be determined in approximately 50% of cases. Here, we report three cases with recurrent ALF caused by NBAS and SCYL1 pathogenic variants. These patients did not present with any other phenotypic sign usually associated with NBAS and SCYL1 pathogenic variants. Two of them underwent liver transplantation and are healthy without recurrence of ALF. We propose NBAS and SCYL1 genetic analysis in children with unexplained fever-triggered recurrent ALF even without a typical phenotype.

Fibrin glue application in the management of refractory chylous ascites in children.

The purpose of this retrospective review of the charts of 6 children who underwent surgical treatment of chylous ascites refractory to conservative measures between 1993 and 2006 was to evaluate the efficiency of fibrin glue application for control of lymph leakage. Five children had postoperative chylous ascites (neuroblastoma, 4; cystic lymphangioma, 1) and 1 had a congenital malformation. Surgical exploration revealed large areas of diffuse lymphatic leakage in all of the patients. Lymphatic fistula was not identified intraoperatively in any patient. Ingestion of lipophilic dye in a concentrated fatty meal was not helpful in locating a lymph fistula. Absorbable mesh was used in association with glue application in the last 3 patients treated. Control of ascites was achieved immediately in 2 patients and within 3 weeks in 2 patients. Repeat surgery was required in the remaining 2 patients. The mean follow-up time was 4.3 years. One patient died of tumor recurrence 12 months after surgical treatment without relapse of the ascites. Two mild late recurrences were observed at 6 and 11 months after surgery and were managed conservatively. The findings of this study show that fibrin glue application on absorbable mesh after dissection of the leakage zones is easy, safe, and effective. We recommend that surgery with glue application be repeated until control of ascites is achieved. We suggest fibrin glue application as a preventive measure against postoperative chylous ascites.

Doppler ultrasound in the diagnosis of Budd-Chiari syndrome in children after split liver transplantation.

PURPOSE: To assess the capabilities of a velocity ratio>3 for the diagnosis of Budd-Chiari syndrome (BCS) in children after split liver transplantation using Doppler ultrasonography (DUS). MATERIALS AND METHODS: A total of 28 children who underwent liver transplantation using a split procedure were included. There were 11boys and 17girls with a mean age of 3.8years (range: 0.7-12years). Velocity ratio between blood velocity upstream of the anastomosis and that at the level of the inferior vena cava anastomosis was calculated. Sensitivity, specificity and accuracy of DUS for the diagnosis of BCS were estimated using a velocity ratio>3. RESULTS: Eight children (8/28; 29%) had BCS and 20 (20/28; 71%) did not have BCS using the standard of reference. A velocity ratio>3 on DUS yielded 88% sensitivity (95% CI: 53-98%), 80% specificity (95% CI: 58-92%) and 82% accuracy (95% CI: 64-92%) for the diagnosis of BCS. CONCLUSION: A velocity ratio>3 on DUS is a reliable finding for the diagnosis of BCS in children after split liver transplantation.

[NISCH syndrome, a rare cause of neonatal cholestasis: A case report]. / Le syndrome NISCH, une cause rare de cholestase néonatale : à propos d'un cas.

NISCH syndrome is a rare autosomal recessive disease. It is characterized by scalp hypotrichosis, scarring alopecia, ichthyosis, and neonatal sclerosing cholangitis. It is caused by mutations in the CLDN1 gene encoding the claudin-1 protein, which is located at tight junctions. Fifteen cases have been reported to date and three different mutations have been identified. We report on the case of a 2-year-old boy from a consanguineous Moroccan family, presenting with NISCH syndrome and carrying the so-called Moroccan homozygous mutation (c.200-201delTT). The patient presented with the characteristic symptoms of the syndrome and a favorable progression with normalization of hepatic analyses under symptomatic treatment (vitamin supplementation and ursodeoxycholic acid). The currently limited availability of clinical and therapeutic data does not allow accurate prediction of the course of the disease and short- and long-term prognosis. Moreover, substantial interindividual variability has been reported. Description of new cases will provide new insights into the understanding and the overall management of this syndrome, the course of which remains elusive.

Molecular effects of cyclosporine and oncogenesis: a new model.

Cyclosporine A is the most commonly used immunosuppressive agent during organ transplantation. One of the most feared adverse effects of cyclosporine A is the appearance of de novo cancers. The mechanisms that lead to the genesis of such cancers are thought to be only related to a side effect of cyclosporine A: a depressed immune system. Here, we review different molecular effects induced by cyclosporine A (inhibition of DNA repair, synthesis of TGF Beta, induction of apoptosis of activated T cells, inhibition of apoptosis through the inhibition of the opening of the mitochondrial Permeability Transition Pore) and propose that cyclosporine A can promote the genesis and the spread of cancer not only because of immunosuppression but also because of its ability to facilitate DNA mutations accumulation, to diminish the clearance of altered cells and to transform cancer cells into aggressive cancer cells. This new insights into the mechanisms of genesis of cyclosporine A-related cancers should be taken into account to develop preventive strategies or new immunosuppressive strategies.

[Oxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure]. / Oxcarbazépine et syndrome DRESS: un cas pédiatrique révélé par une hépatite fulminante.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, also called hypersensitivity reaction, is a severe idiosyncratic reaction to drugs, especially to anti-epileptic drugs. Clinical features associate cutaneous eruption, fever, multiple peripheral ganglions, and potentially life-threatening damage of one or more organs. DRESS syndrome is well described in adults treated with aromatic anti-epileptic drugs, such as phenytoin, phenobarbital, and carbamazepine, but also with other drugs. The new anti-epileptic drugs, such as oxcarbazepine also induce various cutaneous eruptions, but with less report of DRESS syndrome. In children, DRESS syndrome is rare and probably underdiagnosed. We report on the case of a 11-year-old girl hospitalised with an acute severe hepatitis revealing an oxcarbazepine-induced DRESS syndrome.

[Atypical sonographic findings of bacterial colitis]. / Presentation echographique trompeuse de colite infectieuse chez l'enfant.

We report three pediatric cases of infectious colitis that were misinterpreted on US examination as Crohn's disease. These colitis were limited to the left colon and presented with transmural hypoechoic thickening of the wall and homogenous hyperechoic appearance of the surrounding fat.

[Recurrent tracheoesophageal fistula in type III esophageal atresia. Diagnosis and treatment are not easy]. / Reperméation de fistule œso-trachéale dans l'atrésie de l'œsophage de type III : un diagnostic et une prise en charge difficile.

Recurrent tracheoesophageal fistula (TEF) is possible after repair of congenital esophageal atresia. The frequency of recurrent TEF is observed in about 10% of the cases. Within a cohort of 67 children with type III esophageal atresia repaired between 1998 and 2009, we aimed to identify the number of children with recurrent TEF, the risk factors for this condition, and the treatment proposed. The sex ratio was 1.7. Surgery was performed between 4 and 36 hours of life. Five children (7.5%) had a recurrent TEF, usually during the first 3 months, revealed by respiratory symptoms related to feeding in some cases. We noted that recurrent TEF was more frequent with anastomotic leakage (P=0.09) or postsurgical pneumothorax (P<0.01). The diagnosis was made in four cases out of five by a methylene blue test performed during a tracheobronchial endoscopy. Surgical treatment was noted in four children, with three postsurgical secondary effects. One child was treated by endoscopy and an esophageal clip. With a median follow-up of 52 months, no recurrence was noted. The recurrence of TEF may be linked to postsurgical events. Diagnosis is not easy and treatment is not clearly codified. Endoscopic treatment may be an advantageous option to surgery, likely with less morbidity.

Fulminant Hepatitis Due to Father-to-Newborn Transmission of Herpes Simplex Virus type 1.

We describe a case of a severe neonatal infection by herpes simplex virus (HSV) type 1 acquired postnatally from his father. The delivery and the first days of life were normal. He developed liver failure and disseminated intravascular coagulation when he was 19 days old. He was treated with intravenous acyclovir and the outcome was favorable. This case underlines that prevention of post-natal transmission of HSV merits to be considered in educational pregnancy programs directed at mothers and fathers.

[Vitamin K deficiency bleeding: a case secondary to transient neonatal cholestasis]. / Maladie hémorragique par déficit en vitamine K : à propos d'un cas secondaire à une cholestase néonatale transitoire.

We report the case of late vitamin K deficiency bleeding (VLDB), with appropriate but insufficient prophylaxis, secondary to extrahepatic cholestasis. Late VKDB is rare today but serious, with a risk of intracranial hemorrhage in more than half of the cases. The diagnosis, causes and prevention of this disease are discussed.

Fatal case of Reye's syndrome associated with H3N2 influenza virus infection and salicylate intake in a 12-year-old patient.

We describe a fatal case of Reye's syndrome in a 12-year-old male patient during an influenza A (H3N2) infection for which he received salicylates. In the current situation of the novel A/H1N1 virus pandemic, we believe that it is of high importance to emphasize the risks associated with salicylate intake to avoid the reappearance of Reye's syndrome.

Successful treatment of severe cardiomyopathy with NTBC in a child with tyrosinaemia type I.

We report the case of a child who developed severe obstructive hypertrophic cardiomyopathy revealing hereditary tyrosinaemia type I, who was successfully treated with NTBC. The mechanisms underlying the association are discussed.

The cholecystocolic bypass with jejunal interposition graft for bile acid depletion in bile and portal blood in guinea pigs.

Ileal bypass and cholecystostomy are used in children with selected cholestatic diseases to lower the bile acid (BA) levels in bile and blood and improve outcome. The efficacy of a cholecystocolic bypass in achieving the same goals was investigated in guinea pigs. In the study group (n=7), a cholecystocolic bypass was performed using a jejunal graft interposed between the gallbladder and the cecum. In the control group (n=5), a cholecystojejunal bypass was performed with a similar graft implanted in the proximal jejunum. Total BA concentration was measured in bile and portal blood at surgery (D0) and 30 days later (D30) by pooling the concentrations of 7 individual BA. D30/D0 BA ratios were compared. All animals developed normally without clinical symptoms. A 76% reduction in the bile T-BA levels was observed in both groups (p<0.05). A 80% decrease of T-BA levels was observed in portal vein in study group (p<0.05), suggesting that ileal bile flow and BA ileal reabsorption were highly impaired. No change in portal vein BA levels was observed in control group. Cholecystocolic bypass led to a significant loss of bile acids in guinea pigs and might be considered for bile diversion in pediatric patients with selected cholestatic diseases.