Severe Neonatal Metabolic Decompensation in Methylmalonic Acidemia Caused by CblD Defect.

CblD disorder is an autosomal recessive, rare, heterogeneous disease with variable clinical presentations, depending on the nature and location of the MMADHC gene mutations. Mutations in MMADHC lead to three distinct phenotypes: cblD-MMA, cblD-HC, and cblD-MMA/HC. To date, 18 cblD patients have been reported. Six of them were affected by cblD-MMA, but only three had a known clinical history. One of these patients presented with a metabolic decompensation at 11 months; the second one, born prematurely, was diagnosed with cblD after being treated for intracranial hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and convulsions at birth; the third one was diagnosed at 5 years of age.Here we present a case of a cblD-MMA patient who had an acute neonatal onset with severe hyperammonemia requiring hemodiafiltration. To the best of our knowledge, this is the first cblD-MMA patient who presented acutely in the newborn period. He has developed well upon treatment with B12, carnitine, and hypoproteic diet. At present time, at the age of 7, he shows normal growth and cognitive development. Thus, it is likely that the aggressive treatment of this child with hemodiafiltration might have prevented him from long-term neurological sequelae. Overall, this case shows that even severe, neonatal-onset patients may display a vitamin B12-responsive MMA. Furthermore, it suggests that an early treatment with vitamins might be beneficial for patients presenting with neonatal-onset hyperammonemia regardless of the suspected disease and before receiving the biochemical diagnosis.

The impact of perioperative transfusion of blood products on survival after pediatric liver transplantation.

Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after LT in adult patients. This relationship in pediatric patients has not been studied in depth, and its analysis is the scope of this study. Forty-one variables associated with outcome, including blood product transfusions, were studied in a cohort of 243 pediatric patients undergoing a cadaveric LT between 2002 and 2009 at the General Hospital of Bergamo. Multivariate stepwise Cox proportional hazards models were adopted with adjustment by propensity scores to minimize factors associated with the use of blood products. Median age at transplant was 1.37 yr. In uni- and multivariate analyses, perioperative transfusion of FFP and RBC was an independent risk factor for predicting one-yr patient and graft survival. The effect on one-yr survival was dose-related with a hazard ratio of 3.15 for three or more units of RBC (p = 0.033) and 3.35 for three or more units of FFP (p = 0.021) when compared with 1 or no units transfused. The negative impact of RBC and FFP transfusion was confirmed by propensity score-adjusted analysis. These findings may have important implications for transfusion practice in the LT pediatric recipients.

Early detection of the graft failure after pediatric liver transplantation: a Bergamo experience.

BACKGROUND: Effective indicators of the early graft failure after pediatric liver transplantation are currently a crucial question. The aim of this study was to analyze retrospectively laboratory parameters that may help anticipate an early graft loss (GL). METHODS: The 131 pediatric liver transplantations, performed in our hospital from January 2002 to December 2005, were reviewed. Post-operative laboratory parameters, collected in the first 36 h of the Paediatric Intensive Care Unit (PICU) stay, were analyzed for children with both graft survival and GL. Receiver operating characteristics analysis was used to identify the optimal cut-off for the laboratory parameters. Multivariate logistic regression analysis was used to calculate the adjusted risk of GL for the prognostic parameters identified. RESULTS: The mean age at transplant was 1.1 years. The two groups were comparable for all recipient and donor variables considered. Children with GL showed significantly higher levels of ammonia and transaminase at the admission to the PICU and higher levels of prothrombin time, creatinine, lactate and a lower level of platelets at the 36 h of PICU. The laboratory parameters over the cut-off value by the multivariate logistic regression identified all early thromboses earlier than Doppler ultrasound. CONCLUSIONS: This study suggests that routine blood tests may help to anticipate an early loss of liver grafts in children after transplantation and may improve our diagnostic investigation in the case of thrombosis suspicion. Further validation by a prospective study is needed to carefully assess the sensitivity and specificity of the identified criteria.

Transplantation for acute liver failure in children.

We reviewed the clinical data of 30 children-hospitalized for acute liver failure in the last 6 years. Ten patients were not listed for liver transplantation OLTX. Their clinical conditions gradually improved and they are all alive without deficit. Among 20 patients listed, 15 underwent urgent OLTX. Two children died on the waiting list and three were suspended from waiting list after few days because of improvement. Survival according to age class was analyzed dividing the patients into two groups: A, age 1 year or less versus B, age between 1 and 16 years. The patient survival was 86% at 6 months and 61% both at 1 and 2 years. Survival at 6 months and 1 and 2 years was 88%, 67%, and 45% for the patients in group A and 83%, 83%, and 83% for the patients in group B (P = NS). Observing graft-to-recipient weight ratio and donor-to-recipient weight ratio most patients received an optimal sized graft. The split-liver technique is considered the preferred method of liver transplantation even in the pediatric patients with acute liver failure; especially in the setting of a cooperative system in which all livers that are suitable for split-liver transplantation are shared between centers. In order to have the best chance for survival, children with acute liver failure should be referred as soon as possible to an highly specialized pediatric liver transplantation center that can offer all the treatment modalities that are currently available.