Early Liver Transplantation for Neonatal-Onset Methylmalonic Acidemia

American Academy of Pediatrics (AAP) - Tập 136 Số 1 - Trang e252-e256 - 2015
Marco Spada1, Pier Luigi Calvo2, Andrea Brunati3, Licia Peruzzi4, Dominic Dell Olio5, Renato Romagnoli6, Francesco Porta1
1Department of Pediatrics
2aDepartment of Pediatrics,
3Liver Transplant Center, General Surgery 2U, and.
4Nephrology, Dialysis and Transplantation Unit, Regina Margherita Hospital, Turin, Italy.
5Regional Transplant Center, University of Torino, Turin, Italy; and.
6bLiver Transplant Center, General Surgery 2U, and

Tóm tắt

With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalamin-unresponsive methylmalonyl-CoA mutase (MCM) deficiency is characterized by the persistent risk of recurrent life-threatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the last 2 decades with inconsistent results. Most criticisms of this approach have been directed at the continuing risk of neurologic and renal damage after transplant. Here, we report the perioperative and postoperative clinical and biochemical outcomes of 2 patients with severe MCM deficiency who underwent early liver transplant. In both cases, liver transplant allowed prevention of decompensation episodes, normalization of dietary protein intake, and a marked improvement of quality of life. No serious complications have been observed at 12 years’ and 2 years’ follow-up, respectively, except for mild kidney function impairment in the older patient. On the basis of our experience, we strongly suggest that liver transplant should be offered as a therapeutic option for children with cobalamin-unresponsive MCM deficiency at an early stage of the disease.

Từ khóa


Tài liệu tham khảo

Fernandes, 2006, Inborn Metabolic Diseases: Diagnosis and Treatment, 4th ed., 10.1007/978-3-540-28785-8

van der Meer, 1994, Clinical outcome of long-term management of patients with vitamin B12-unresponsive methylmalonic acidemia., J Pediatr, 125, 903, 10.1016/S0022-3476(05)82005-0

Nicolaides, 1998, Neurological outcome of methylmalonic acidaemia., Arch Dis Child, 78, 508, 10.1136/adc.78.6.508

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

Goyens, 1997, Liver transplantation for methylmalonyl-CoA mutase deficiency., J Inherit Metab Dis, 20, 39

Chakrapani, 2002, Metabolic stroke in methylmalonic acidemia five years after liver transplantation., J Pediatr, 140, 261, 10.1067/mpd.2002.121698

Kayler, 2002, Long-term survival after liver transplantation in children with metabolic disorders., Pediatr Transplant, 6, 295, 10.1034/j.1399-3046.2002.02009.x

Leonard, 2001, The management of organic acidaemias: the role of transplantation., J Inherit Metab Dis, 24, 309, 10.1023/A:1010395724012

Nyhan, 2002, Progressive neurologic disability in methylmalonic acidemia despite transplantation of the liver., Eur J Pediatr, 161, 377, 10.1007/s00431-002-0970-4

Nagarajan, 2005, Management of methylmalonic acidaemia by combined liver–kidney transplantation., J Inherit Metab Dis, 28, 517, 10.1007/s10545-005-0517-8

Morioka, 2007, Efficacy of living donor liver transplantation for patients with methylmalonic acidemia., Am J Transplant, 7, 2782, 10.1111/j.1600-6143.2007.01986.x

de Baulny, 2005, Methylmalonic and propionic acidaemias: management and outcome., J Inherit Metab Dis, 28, 415, 10.1007/s10545-005-7056-1

Andrews, 1993, Expression of recombinant human methylmalonyl-CoA mutase: in primary mut fibroblasts and Saccharomyces cerevisiae., Biochem Med Metab Biol, 50, 135, 10.1006/bmmb.1993.1055

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

Kasahara, 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

Chen, 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

Wilnai, 2014, Abnormal hepatocellular mitochondria in methylmalonic acidemia., Ultrastruct Pathol, 38, 309, 10.3109/01913123.2014.921657

Vernon, 2014, A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut (0) methylmalonic acidemia., J Inherit Metab Dis, 37, 899, 10.1007/s10545-014-9730-7

Morioka, 2005, Living donor liver transplantation for noncirrhotic inheritable metabolic liver diseases: impact of the use of heterozygous donors., Transplantation, 80, 623, 10.1097/01.tp.0000167995.46778.72

Lubrano, 2013, Methylmalonic acidemia and kidney transplantation., Pediatr Nephrol, 28, 2067, 10.1007/s00467-013-2536-2

Brassier, 2013, Renal transplantation in 4 patients with methylmalonic aciduria: a cell therapy for metabolic disease., Mol Genet Metab, 110, 106, 10.1016/j.ymgme.2013.05.001

Kaplan, 2006, Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency., Mol Genet Metab, 88, 322, 10.1016/j.ymgme.2006.04.003

Macchiaiolo, 2012, Too late to say it is too early—how to get children with non-cirrhotic metabolic diseases transplanted at the right time?, Pediatr Transplant, 16, 671, 10.1111/j.1399-3046.2011.01623.x

Perito, 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

Hadžić, 2014, The times they are a-changin’., Liver Transpl, 20, 1, 10.1002/lt.23802

Salizzoni, 2005, The first one thousand liver transplants in Turin: a single-center experience in Italy., Transpl Int, 18, 1328, 10.1111/j.1432-2277.2005.00215.x

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

Thông tin
Thông tin xuất bản

American Academy of Pediatrics (AAP)

Tập 136 Số 1

e252-e256

Thông tin tác giả