Kidney disease and organ transplantation in methylmalonic acidaemia.

OBJECTIVES: MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre-, peri-, and post-transplant course of all children with MMA who underwent liver or combined liver-kidney transplant in our centers. DESIGN AND METHODS: Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years. RESULTS: Five children with MMA underwent liver transplant (4/5) and combined liver-kidney transplant (1/5). Three were Mut0 and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post-transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine-based GFR formula. We noticed in 2 patients a big discrepancy between creatinine- and cystatin C-based GFR calculations. One patient with no renal disease developed renal failure post-liver transplantation. Serum MMA levels have decreased in all to <300 µmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post-transplant. CONCLUSIONS: MMA is a complex metabolic disorder. Renal disease can continue to progress post-liver transplant and close follow-up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post-transplant can halt the progression of renal disease remains unclear.

Early critical care course in children after liver transplant.

Objective. To review the critical care course of children receiving orthotopic liver transplantation (OLT). Methods. A retrospective chart review of patients admitted to the pediatric critical care following OLT performed in our center between 1988 and 2011. Results. A total of 149 transplants in 145 patients with a median age of 2.7 (IQR 0.9-7) years were analyzed. Mortality in the first 28 days was 8%. The median length of stay (LOS) was 7 (4.0-12.0) days. The median length of mechanical ventilation (MV) was 3 (1.0-6.2) days. Open abdomen, age, and oxygenation index on the 2nd day predicted LOS. Open abdomen, age, amount of blood transfused during surgery, and PRISM III predicted length of MV. 28% of patients had infection and 24% developed acute rejection. In recent group (2000-2011) OLT was performed in younger patients; the risk of infection and acute rejection was reduced and patients required longer LOS and MV compared with old group (1988-1999). Conclusion. The postoperative course of children after OLT is associated with multiple complications. In recent years OLT was performed in younger children; living donors were more common; the rate of postoperative infection and suspected rejection was reduced significantly; however patients required longer MV and LOS in the PCCU.

Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.

Mitochondrial depletion syndrome (MDS) refers to a heterogeneous group of mitochondrial disorders characterized by a reduction of the mtDNA copy number in affected tissues. Mutations in DGUOK encoding deoxyguanosine kinase (MIM 601465) cause the hepatocerebral form of MDS (MIM 251880). Cystathioninuria (MIM 219500) can result from mutations in CTH encoding cystathionine gamma lyase (MIM 607657) or can be a secondary finding in several diverse clinical conditions. We present three patients from two apparently unrelated old colony Mennonite families, each of whom had the hepatocerebral form of MDS together with cystathioninuria. Each affected child was homozygous for the novel DGUOK p.D255Y mutation, but had no CTH mutation, indicating that the hepatocerebral form of MDS might be associated with secondary cystathioninuria.

Cavoportal transposition for portal vein thrombosis in a pediatric living-related liver transplantation.

We report a case of a living-related liver transplantation in a child in whom diffuse thrombosis of the portal venous system required the use of recipient vena cava to perfuse the donor portal vein (cavoportal transposition). An 8 (1/2)-month-old infant with biliary atresia received the left lateral segment of his father's liver. The child's portal vein was irretrievably thrombosed, as were the splenic and superior mesenteric veins. A cavoportal anastomosis provided excellent flow to the liver, and there was no engorgement of the graft, which had good immediate function. The main postoperative problem was loss of 3 to 3.5 liters of ascitic fluid through the drain for 2 weeks. The ascites eventually resolved over a period of 4 weeks. Twenty-four months after transplantation, the child is thriving on a normal diet and has no ascites. A Doppler examination showed good flow in the cavoportal anastomosis.

Long-term results of pediatric liver transplantation in a combined pediatric and adult transplant program.

BACKGROUND: Liver transplantation is now routine therapy for a variety of childhood liver diseases; however, there are no detailed reports of long-term results from a Canadian centre. We reviewed data from the first 16 years of a pediatric liver transplantation program to determine survival, complications and long-term outcomes. METHODS: The outcomes to December 2000 for all children (age less than 18 years) who received a liver transplant at the London Health Sciences Centre between April 1984 and December 1999 were reviewed. The recipients were grouped according to the period in which they received the transplant (period 1, April 1984 to July 1988; period 2, August 1988 to December 1993; or period 3, January 1994 to December 1999). Data were obtained from medical charts; in-person interviews, questionnaires or telephone contact with patients and their families; contact with referring physicians; and school records. Outcome measures included patient survival, retransplantation, complications and long-term outcomes (specifically steroid withdrawal and growth and development). RESULTS: A total of 116 children (29 in period 1, 46 in period 2 and 41 in period 3) (median age 5.6 years at the time of the procedure) received a total of 140 liver grafts (32 in period 1, 57 in period 2 and 51 in period 3). Of the 116 patients, 23 (20%) were less than 1 year old at the time of transplantation. Biliary atresia was the most common indication for liver transplantation (57 [49%] of the 116 patients). The number of patients surviving to 1 year after transplantation was 20 (69%) of the 29 patients from period 1, 40 (87%) of the 46 patients from period 2 and 38 (93%) of the 41 patients from period 3. The percentage of patients receiving reduced size grafts from adult donors, including live donors, increased from 2/32 (6%) in period 1 to 22/51 (43%) in period 3. Retransplantation was required for 9 (31%) of the 29 patients from period 1, 6 (13%) of the 46 patients from period 2 and 7 (17%) of the 41 patients from period 3. Among these patients, 1-year survival was 33% (3/9) for period 1, 83% (5/6) for period 2 and 100% (7/7) for period 3. Eighteen of the 22 deaths occurred within 4 months after surgery. Only 3 (3%) of the 116 patients experienced post-transplant lymphoproliferative disease. Steroids were discontinued (usually within 2 years after surgery) for the following proportions of surviving transplant recipients: 17 (89%) of the 19 patients from period 1, 29 (78%) of the 37 patients from period 2 and 21 (55%) of the 38 patients from period 3. Most of the surviving patients had normal growth (82/94 or 87%) and development (73/94 or 78%), and these outcomes were consistent across the 3 periods of study. INTERPRETATION: Survival and long-term outcomes continue to improve for most children who receive liver transplants. These improvements may be due to improved surgical technique, perioperative care and, to a lesser extent, immunosuppressive therapy.