Abstracts

LIVER TRANSPLANTATION (LT) FOR MAPLE SYRUP URINE DISEASE (MSUD): PROTOCOL AND PRELIMINARY RESULTS.

G. Mazariegos, H. Morton, K. Strauss, R. Squires, D. Finegold, M. Virgi, L. Cropcho, Erik Puffenberger, W. McGhee, L. Seward, R. Sindhi. Starzl Transplantation Institute, Pittsburgh, PA; Transplant Surgery, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA; Clinic for Special Children, Strasburg, PA.

Aim: Case reports of cure of MSUD by LT prompted a systematic evaluation of the effects of LT in these patients.

Methods: Preoperative protocol included minimization of pre-transplant fasting, dextrose infusion rates > 7 mg/kg-min to suppress endogenous protein catabolism, and strict sodium and water homeostasis. Amino acid profiles (AAP) were sent at baseline and regularly post LT with dietary protein intake recorded.

Results: 6 children (age 1.9–8.4 years) with severe, or Classical, biochemical phenotype underwent LT. Patient 1 was transplanted for hypervitaminosis A-associated liver failure. The five younger patients were electively transplanted to achieve metabolic cure. All patients are alive and well with follow-up from 3 months to 7.5 years. AAPs on an unrestricted diet were available for Pt #1 for >100 month follow-up. All leucine, isoleucine, and valine levels normalized immediately post LT and maintained normal parameters despite an unrestricted protein intake. Metabolic cure was documented by 1) a sustained increase in weight-adjusted leucine tolerance from 15–20 mg/kg-day to > 150 mg/kg-day 2) normalization of molar ratios among the BCAAs, demonstrating in vivo regulation of amino acid oxidation rates (FIG. 1), and 3) metabolic stability during intercurrent illnesses.

Conclusion: This series of children successfully transplanted for MSUD demonstrates metabolic cure, with removal of dietary restrictions and complete protection from decompensation during illness. Preliminary observations suggest an improvement in long-term neurodevelopmental outcome that will be confirmed by prospective evaluation.