Domino liver transplantation in maple syrup urine disease

Abstract

Liver transplantation has been reported in a few cases of maple syrup urine disease (MSUD), but is controversial. Many patients with approved indications for liver transplantation die before grafts are available. A 25-yr-old man with MSUD underwent liver transplantation, and his liver was used as a domino graft for a 53-yr-old man with hepatocellular carcinoma who had low priority on the liver transplant waiting list and was unlikely to survive until routine organ procurement. Both transplants were performed as "piggy back" procedures, reconstructing the domino graft with caval segments from the cadaveric donor. Neither required veno-venous bypass. Whole body leucine oxidation was estimated by 13 CO 2 in breath after oral boluses of L-[1-13 C]-leucine, before and after transplantation in both patients and a control subject. The surgical outcome was successful. The patient with MSUD had marked decreases in plasma branched-chain amino acids (BCAAs) and alloisoleucine (from 255 Ϯ 66 to 16 Ϯ 7 mol/L), despite advancement of dietary protein from 6 to Ͼ40 gm/day. The domino recipient maintained near-normal levels of plasma amino acids with no detectable alloisoleucine on unrestricted diet. Leucine oxidation increased in the patient with MSUD (from 2.2 to 5.6% recovered in 4 hours) and decreased in the recipient (from 9.7 to 6.2%). Neither patient demonstrated any apparent symptoms of MSUD over more than 7 months. In conclusion, liver transplantation substantially corrects whole body BCAA metabolism in MSUD and greatly attenuates the disease. Livers from patients with MSUD may be considered as domino grafts for patients who might otherwise not survive until transplantation. Liver Transpl 12: 876 -882, 2006.

Successful domino liver transplantation in maple syrup urine disease using a related living donor

“…Domino livers were first considered as marginal grafts because the disease could manifest in the domino recipient (9). However, recipients of liver grafts from MSUD donors will probably not develop protein intolerance because 60% of BCKDH activity occurs in the muscle.…”

Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes

“…Affected individuals can have mild steatosis and transaminitis but maintain normal synthetic liver function[2]. However, when these patients have undergone hepatic transplantation, the native livers have not been used in a domino fashion, as has been done in other metabolic disorders of branched chain aminoacid oxidation, such as maple syrup urine disease[41]. Most methymalonic acidemia patients undergoing liver transplantation will have the organ harvested and discarded or sent to pathology.…”

Surgical gene therapy by domino auxiliary liver transplantation

“…In the recipient of domino LT, the enzymatic pathway defective in the graft is corrected by normal extrahepatic tissue that provides enough wild-type enzyme to compensate the metabolic defect. 7 In this issue of Liver Transplantation, Govil et al 8 introduce a new transplant strategy for the treatment of monogenic liver disease, combining the APOLT technique with the domino tactic in 2 children with different metabolic defects: 1 expressed also by extrahepatic tissue (PA) and 1 confined to the liver (CN1). The child with PA received an APOLT from his (heterozygous) mother, whereas the child with CN1 received a domino APOLT from the partial hepatectomy of the child with PA.…”