Liver transplantation in propionic and methylmalonic acidemia: A single center study with literature review

Nishitha R. Pillai, Bridget M. Stroup, Anna Poliner, Linda Rossetti, Brandy Rawls, Brian J. Shayota, Claudia Soler-Alfonso, Hari Priya Tunuguntala, John Goss, William Craigen, Fernando Scaglia, V. Reid Sutton, Ryan Wallace Himes, Lindsay C. Burrage

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Organic acidemias, especially propionic acidemia (PA) and methylmalonic acidemia (MMA), may manifest clinically within the first few hours to days of life. The classic presentation in the newborn period includes metabolic acidosis, hyperlactatemia, and hyperammonemia that is precipitated by unrestricted protein intake. Implementation of newborn screening to diagnose and initiate early treatment has facilitated a reduction in neonatal mortality and improved survival. Despite early diagnosis and appropriate management, these individuals are prone to have recurrent episodes of metabolic acidosis and hyperammonemia resulting in frequent hospitalizations. Liver transplantation (LT) has been proposed as a treatment modality to reduce metabolic decompensations which are not controlled by medical management. Published reports on the outcome of LT show heterogeneous results regarding clinical and biochemical features in the post transplantation period. As a result, we evaluated the outcomes of LT in our institution and compared it to the previously published data. Study design/methods: We performed a retrospective chart review of nine individuals with PA or MMA who underwent LT and two individuals with MMA who underwent LT and kidney transplantation (KT). Data including number of hospitalizations, laboratory measures, cardiac and neurological outcomes, dietary protein intake, and growth parameters were collected. Results: The median age of transplantation for subjects with MMA was 7.2 years with a median follow up of 4.3 years. The median age of transplantation for subjects with PA was 1.9 years with a median follow up of 5.4 years. The survival rate at 1 year and 5 years post-LT was 100%. Most of our subjects did not have any episodes of hyperammonemia or pancreatitis post-LT. There was significant reduction in plasma glycine post-LT. One subject developed mild elevation in ammonia post-LT on an unrestricted protein diet, suggesting that protein restriction may be indicated even after LT. Conclusion: In a large single center study of LT in MMA and PA, we show that LT may reduce the incidence of metabolic decompensation. Moreover, our data suggest that LT may be associated with reduced number of hospitalizations and improved linear growth in individuals with PA and MMA.

Original languageEnglish (US)
Pages (from-to)431-443
Number of pages13
JournalMolecular Genetics and Metabolism
Volume128
Issue number4
DOIs
StatePublished - Dec 2019
Externally publishedYes

Bibliographical note

Funding Information:
NRP is supported by Sanofi Genzyme ACMGF Next Generation Training Award . LCB is supported by NIH K08DK106453 and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund . BMS is supported by NIH T32DK007664-28 (BS) and the US Public Health Service grant P30DK56338 , which funds the Texas Medical Center Digestive Disease Center. BJS is supported by the Takeda Next Generation Medical Biochemical Subspecialty Fellowship .

Funding Information:
NRP is supported by Sanofi Genzyme ACMGF Next Generation Training Award. LCB is supported by NIH K08DK106453 and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. BMS is supported by NIH T32DK007664-28 (BS) and the US Public Health Service grant P30DK56338, which funds the Texas Medical Center Digestive Disease Center. BJS is supported by the Takeda Next Generation Medical Biochemical Subspecialty Fellowship.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Liver transplantation
  • Methylmalonic acidemia
  • Organic acidemia
  • Propionic acidemia

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