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

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

Author information

1
Hospital Sirio Libanes, São Paulo, Brazil; Hospital Santa Casa de Misericórdia, Porto Alegre, Brazil.
2
Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil; Genetics Department, Universidade Federal do Rio Grande do Sul, Brazil.
3
Clinic for Special Children, Strasburg, PA, USA.
4
Hospital Sirio Libanes, São Paulo, Brazil.
5
Pediatrics Department, Universidade Federal do Rio Grande do Sul, Brazil; Pediatrics Liver Transplantation Program, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
6
Pediatrics Liver Transplantation Program, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
7
Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil.
8
Pediatrics Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
9
Hillman Center for Pediatric Transplantation, Children's Hospital of UPMC, Pittsburgh, PA, USA.
10
Clinic for Special Children, Strasburg, PA, USA; Franklin & Marshall College, Lancaster, PA, USA.
11
Clinic for Special Children, Strasburg, PA, USA; Franklin & Marshall College, Lancaster, PA, USA; Lancaster General Hospital, Lancaster, PA, USA. Electronic address: kstrauss@clinicforspecialchildren.org.

Abstract

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

PMID:
26786177
DOI:
10.1016/j.ymgme.2016.01.005
[Indexed for MEDLINE]

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