Ascites in infantile onset type II Sialidosis.

Sialidosis is a rare autosomal-recessive lysosomal storage disease due to mutations in the NEU1 gene leading to a deficit of alpha-n-acetyl neuraminidase and causing aberrant accumulation of sialylated glycoproteins/peptides and oligosaccharides in the lysosomes of various organs and tissues. Type II sialidosis (dysmorphic form) is classified into three subgroups based on the age of onset and the clinical severity: Congenital or neonatal, infantile (onset 0-12 months) and juvenile form (onset 13 months-20 years). We report the case of a 3-year-old boy with sialidosis type II infantile form, who developed a voluminous ascites. To the best of our knowledge, ascites is not described in the infantile form but in the congenital form of the disease. Ascites seems to be of a multifactorial origin regarding our investigations: on the one hand, portal hypertension and on the other hypoalbuminemia maintained by proteinuria secondary to nephrosialidosis. Loss of plasma proteins in the gastrointestinal tract (protein-losing enteropathy) should also be considered in the case of portal hypertension and damages of the reticuloendothelial system.

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

OBJECTIVES: To evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein (PV) reconstruction, ABO compatibility, and impact of maternal donation on graft acceptance. BACKGROUND: LDLT and ABO-mismatched transplantation constitute feasible options to alleviate organ shortage in children. Vascular complications of portal hypoplasia in biliary atresia (BA) and acute rejection (AR) are still major concerns in this field. METHODS: Data from 250 pediatric LDLT recipients, performed at Cliniques Universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively. Results were analyzed according to ABO matching and PV complications. Uni- and multivariate analyses were performed to study the impact of immunosuppression, sex matching, and maternal donation on AR rate. RESULTS: Overall, the 10-year patient survival rate was 93.2%. Neither patient or graft loss nor vascular rejection, nor hemolysis, was encountered in the ABO nonidentical patients (n = 58), provided pretransplant levels of relevant isoagglutinins were below 1/16. In BA recipients, the rate of PV complications was lower after portoplasty (4.6%) than after truncal PV anastomosis (9.8%) and to jump graft interposition (26.9%; P = 0.027). In parental donation, maternal grafts were associated with higher 1-year AR-free survival (55.2%) than paternal grafts (39.8%; P = 0.041), but only in BA patients. CONCLUSIONS: LDLT, including ABO-mismatched transplantation, constitutes a safe and efficient therapy for liver failure in children. In BA patients with PV hypoplasia, portoplasty seems to constitute the best technique for PV reconstruction. Maternal donation might be a protective factor for AR.

Prehospital paediatric emergencies in Belgium: an epidemiologic study.

OBJECTIVES: In Belgium, emergency medical services (EMS) are staffed with a medical team if mandatory according to the regulation authority procedures. Children are involved in interventions, but no extensive data are available in the country. We analysed the characteristics of the children involved in EMS to gain better knowledge of the pathologies and the needs of these patients. MATERIALS AND METHODS: A retrospective review of all patients under 16 years of age dealt with by our EMS team during a 2-year period. RESULTS: During the 2010-2011 period, our EMS performed 229 paediatric missions. Most of the patients (76.0%) presented medical conditions. Seizure was the most common diagnosis (34.1%), including febrile convulsions in 55.1% of the cases. Five patients (2.2%) suffered a cardiac arrest. All of them died despite advanced life support. Two more patients died before or just after admission to the emergency room. In the subgroup of patients admitted to our hospital, 26.6% needed drug administration and 43.2% were discharged home after emergency room management. CONCLUSION: Prehospital paediatric emergencies are rarely life-threatening conditions and seldom need advanced medical interventions. However, the outcome of real life-threatening conditions is poor, therefore emphasizing the need for better trained teams.

Influence of donor-recipient CYP3A4/5 genotypes, age and fluconazole on tacrolimus pharmacokinetics in pediatric liver transplantation: a population approach.

AIM: To characterize the effect of donor and recipient CYP3A4, CYP3A5 and ABCB1 genotypes as well as relevant patient characteristics on tacrolimus pharmacokinetics in pediatric liver transplantation. PATIENTS & METHODS: Data from 114 pediatric liver transplant recipients were retrospectively collected during the first 3 months following transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed effects modeling, including characterization of influential covariates. RESULTS: A two-compartment model with first order elimination best fitted the data. Estimates of apparent volume of the central compartment, intestinal clearance, hepatic clearance and intercompartmental clearance were 79 l, 0.01 l/h, 10.9 l/h and 105 l/h, respectively. Time post-transplantation, recipient age, donor CYP3A5 and CYP3A4 genotypes and fluconazole administration significantly influenced tacrolimus apparent clearance while bodyweight influenced volume of distribution. CONCLUSION: The proposed model displayed acceptable fitting performances and enabled identification of statistically significant and clinically relevant covariates on tacrolimus pharmacokinetics in the early pediatric post liver transplantation period.

Population pharmacokinetic analysis of tacrolimus early after pediatric liver transplantation.

BACKGROUND: Tacrolimus (TAC) pharmacokinetics (PKs) show considerable unexplained variability, particularly in the early period after transplantation. Therefore, TAC is a good candidate for therapeutic drug monitoring. The main objective of the present work was to propose a robust PK model for TAC in the early period after transplantation, with the final goal to provide practitioners with a tool for dose individualization in pediatric patients. METHODS: TAC concentration data were obtained from 82 pediatric liver allograft recipients during the first 2 weeks after transplantation. Previously published models, and a model recently developed by our group for pediatrics early after pediatric liver transplantation, were fitted to the data and their predictive performance compared with the performances of a model developed using the data from 82 pediatric patients. RESULTS: During the data-driven analysis, the PKs of TAC were best described by a 1-compartment model with time-varying first order elimination. Apparent volume of distribution and blood clearance estimates were 283 L and 10 L/h, respectively. The absorption was also considered to be a first order process, with a first order rate fixed to 4.45 hours. Parameters were estimated with good precision and accuracy. Although hematocrit levels, time after transplantation, liver weight, and body weight influenced the clearance, body weight was the only covariate retained on volume of central and peripheral compartments. Two of the 5 previous models showed acceptable predictive performances using the observed data. CONCLUSIONS: Time after transplantation, body weight, and hematocrit levels were shown to influence TAC PK in the early pediatric post-liver transplantation period and should be considered, besides therapeutic drug monitoring, by clinicians for the TAC posology prescription and adaptation.