Liver Transplantation for Propionic Acidemia and Methylmalonic Acidemia: Perioperative Management and Clinical Outcomes

Liver Transplantation - Tập 24 Số 9 - Trang 1260-1270 - 2018
Kristen Critelli1, Patrick McKiernan2,1, Jerry Vockley2,3, George Mazariegos2,4, Robert H. Squires2,1, Kyle Soltys2,4, James E. Squires2,1
1Division of Gastroenterology, Hepatology and Nutrition,Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center,Pittsburgh,PA
2Center for Rare Disease Therapy,Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center,Pittsburgh,PA
3Division of Medical Genetics,Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center,Pittsburgh,PA
4Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Department of Transplant Surgery,Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center,Pittsburgh,PA

Tóm tắt

Abstract Propionic acidemia (PA) and methylmalonic acidemia (MMA) comprise the most common organic acidemias and account for profound morbidity in affected individuals. Although liver transplantation (LT) has emerged as a bulk enzyme‐replacement strategy to stabilize metabolically fragile patients, it is not a metabolic cure because patients remain at risk for disease‐related complications. We retrospectively studied LT and/or liver‐kidney transplant in 9 patients with PA or MMA with additional focus on the optimization of metabolic control and management in the perioperative period. Metabolic crises were common before transplant. By implementing a strategy of carbohydrate minimization with gradual but early lipid and protein introduction, lactate levels significantly improved over the perioperative period (P < 0.001). Posttransplant metabolic improvement is demonstrated by improvements in serum glycine levels (for PA; P < 0.001 × 10–14), methylmalonic acid levels (for MMA; P < 0.001), and ammonia levels (for PA and MMA; P < 0.001). Dietary restriction remained after transplant. However, no further metabolic crises have occurred. Other disease‐specific comorbidities such as renal dysfunction and cardiomyopathy stabilized and improved. In conclusion, transplant can provide a strategy for altering the natural history of PA and MMA providing stability to a rare but metabolically brittle population. Nutritional management is critical to optimize patient outcomes.

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Tài liệu tham khảo

2018, Incidence of maple syrup urine disease, propionic acidemia, and mathylmalonic aciduria from newborn screening data, Mol Genet Metab Rep, 15, 106

2016, Methylmalonic and propionic acidemias: clinical management update, Curr Opin Pediatr, 28, 682, 10.1097/MOP.0000000000000422

2006, Clinical approach to treatable inborn metabolic diseases: an introduction, J Inherit Metab Dis, 29, 261, 10.1007/s10545-006-0358-0

2006, Methylmalonic and propionic aciduria, Am J Med Genet C Semin Med Genet, 142C, 104, 10.1002/ajmg.c.30090

2015, Early liver transplantation for neonatal‐onset methylmalonic acidemia, Pediatrics, 136, e252, 10.1542/peds.2015-0175

2014, Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia, Orphanet J Rare Dis, 9, 130, 10.1186/s13023-014-0130-8

2013, Long‐term neurological outcome of a cohort of 80 patients with classical organic acidurias, Orphanet J Rare Dis, 8, 148, 10.1186/1750-1172-8-148

1995, The management and outcome of propionic and methylmalonic acidaemia, J Inherit Metab Dis, 18, 430, 10.1007/BF00710054

2012, Propionic acidemia consensus conference summary, Mol Genet Metab, 105, 3, 10.1016/j.ymgme.2011.08.007

2014, Pediatric liver transplantation for urea cycle disorders and organic acidemias: United Network for Organ Sharing data for 2002–2012, Liver Transpl, 20, 89, 10.1002/lt.23765

2015, Early and late complications after liver transplantation for propionic acidemia in children: a two centers study, Am J Transplant, 15, 786, 10.1111/ajt.13027

2012, Living‐donor liver transplantation for propionic acidemia, Pediatr Transplant, 16, 230, 10.1111/j.1399-3046.2011.01607.x

2011, Liver transplantation for propionic acidemia in children, Liver Transpl, 17, 661, 10.1002/lt.22279

2010, Stabilization of blood methylmalonic acid level in methylmalonic acidemia after liver transplantation, Pediatr Transplant, 14, 337, 10.1111/j.1399-3046.2009.01227.x

2015, Cost‐effectiveness of liver transplantation in methylmalonic and propionic acidemias, Liver Transpl, 21, 1208, 10.1002/lt.24173

1976, A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine, Pediatrics, 58, 259, 10.1542/peds.58.2.259

2015, Treatment of methylmalonic acidemia by liver or combined liver‐kidney transplantation, J Pediatr, 166, 1455, 10.1016/j.jpeds.2015.01.051

2018, Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia, Am J Med Genet A, 176, 687, 10.1002/ajmg.a.38599

2017, The relationship between dietary intake, growth, and body composition in inborn errors of intermediary protein metabolism, J Pediatr, 188, 163, 10.1016/j.jpeds.2017.05.048

2018, Long‐term liver disease in methylmalonic and propionic acidemias, Mol Genet Metab, 123, 433, 10.1016/j.ymgme.2018.01.009

2017, Audit of organic acidurias from a single centre: clinical and metabolic profile at presentation with long term outcome, J Clin Diagn Res, 11, SC11

2014, Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatol Nutr Hepatol, 60, 362

2013, Monogenic diseases that can be cured by liver transplantation, J Hepatol, 59, 595, 10.1016/j.jhep.2013.04.004

2016, Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant, Pediatr Transplant, 20, 1081, 10.1111/petr.12804

2006, Current role of liver transplantation for methylmalonic acidemia: a review of the literature, Pediatr Transplant, 10, 943, 10.1111/j.1399-3046.2006.00585.x

2016, Analysis of factors associated with biliary complications in children after liver transplantation, Transplantation, 100, 1944, 10.1097/TP.0000000000001298

2016, Perioperative management of living‐donor liver transplantation for methylmalonic acidemia, Paediatr Anaesth, 26, 694, 10.1111/pan.12930

2016, Anaesthetic considerations for liver transplantation in propionic acidemia, Indian J Anaesth, 60, 50, 10.4103/0019-5049.174799

2015, Anesthesia and organic aciduria: is the use of lactated Ringer’s solution absolutely contraindicated?, Paediatr Anaesth, 25, 807, 10.1111/pan.12673

2017, Liver transplantation for propionic acidemia, J Pediatr Gastroenterol Nutr, 64, e73

2011, Preoperative dialysis for liver transplantation in methylmalonic acidemia, Ther Apher Dial, 15, 488, 10.1111/j.1744-9987.2011.00974.x

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Liver Transplantation

Tập 24 Số 9

1260-1270

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