Living related versus deceased donor liver transplantation for maple syrup urine disease

Mol Genet Metab. 2016 Mar;117(3):336-43. doi: 10.1016/j.ymgme.2016.01.005. Epub 2016 Jan 12.


Maple syrup urine disease (MSUD) is an inherited disorder of branched chain ketoacid (BCKA) oxidation associated with episodic and chronic brain disease. Transplantation of liver from an unrelated deceased donor restores 9-13% whole-body BCKA oxidation capacity and stabilizes MSUD. Recent reports document encouraging short-term outcomes for MSUD patients who received a liver segment from mutation heterozygous living related donors (LRDT). To investigate effects of living related versus deceased unrelated grafts, we studied four Brazilian MSUD patients treated with LRDT who were followed for a mean 19 ± 12 postoperative months, and compared metabolic and clinical outcomes to 37 classical MSUD patients treated with deceased donor transplant. Patient and graft survival for LRDT were 100%. Three of 4 MSUD livers were successfully domino transplanted into non-MSUD subjects. Following LRDT, all subjects resumed a protein-unrestricted diet as mean plasma leucine decreased from 224 ± 306 μM to 143 ± 44 μM and allo-isoleucine decreased 91%. We observed no episodes of hyperleucinemia during 80 aggregate postoperative patient-months. Mean plasma leucine:isoleucine:valine concentration ratios were ~2:1:4 after deceased donor transplant compared to ~1:1:1.5 following LRDT, resulting in differences of predicted cerebral amino acid uptake. Mutant heterozygous liver segments effectively maintain steady-state BCAA and BCKA homeostasis on an unrestricted diet and during most catabolic states, but might have different metabolic effects than grafts from unrelated deceased donors. Neither living related nor deceased donor transplant affords complete protection from metabolic intoxication, but both strategies represent viable alternatives to nutritional management.

Keywords: Branched chain ketoacid dehydrogenase; Domino transplantation; Living related donor liver transplantation; Maple syrup urine disease.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / blood
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / genetics
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / metabolism
  • Adult
  • Brazil
  • Child
  • Child, Preschool
  • Diet
  • Female
  • Follow-Up Studies
  • Heterozygote
  • Humans
  • Isoleucine / blood
  • Leucine / blood
  • Liver Transplantation*
  • Living Donors*
  • Male
  • Maple Syrup Urine Disease / genetics*
  • Maple Syrup Urine Disease / physiopathology
  • Maple Syrup Urine Disease / surgery*
  • Maple Syrup Urine Disease / therapy
  • Oxidation-Reduction
  • Sequence Analysis, DNA
  • Tissue Donors
  • Treatment Outcome
  • Valine / blood


  • Isoleucine
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Leucine
  • Valine