Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia

Abstract

Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but longterm outcome is controversial. Many patients with other approved indications for liver transplantation die before donor grafts are available. A 28-year-old man with MMA underwent cadaveric liver transplantation. His liver was used as a domino graft for a 61-year-old man with primary sclerosing cholangitis, who had low priority on the transplant waiting list. Surgical outcome was successful, and after transplantation both patients have excellent graft function. The patient with MMA showed substantial decrease in methylmalonate in urine (from 5,277 AE 1,968 preoperatively to 1,068 AE 384 mmol/mol creatinine) and plasma (from 445.9 AE 257.0 to 333.3 AE 117.7 mmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 AE 0.33 g/kg/day. The domino recipient maintained near-normal levels of plasma amino acids but did develop elevated methylmalonate in blood and urine while receiving an unrestricted diet (peak plasma methylmalonate 119 mmol/l and urine methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein). Neither patient demonstrated any apparent symptoms of MMA or metabolic decompensation during the postoperative period or following discharge.Conclusion: Liver transplantation substantially corrects methylmalonate metabolism in MMA and greatly attenuates the disease. In this single patient experience, a liver from a patient with MMA functioned well as domino graft although it did result in subclinical methylmalonic acidemia and aciduria in the recipient. Patients with MMA can be considered as domino liver donors for patients who might otherwise spend long times waiting for liver transplantation.

Technique and outcome of domino liver transplantation from patients with maple syrup urine disease: Expanding the donor pool for live donor liver transplantation

“…We used two reduced grafts and the whole livers were transplanted successfully in other patients. DLT from methyl malonic acidemia donor was first reported by the senior author in 2015 . Despite having normal liver and renal function, elevated plasma and urine levels of methyl malonate were observed, and long‐term results and outcome to see the effect of high unwanted metabolites are pending.…”

“…Consequently, these organs are transplanted for select indications, mostly in adult recipients, as marginal grafts . Recent reports with long‐term follow‐up have demonstrated long‐term safety of DLT from patients with MSUD especially in the pediatric recipients of domino livers …”

Evolving Trends in Liver Transplant for Metabolic Liver Disease in the United States

“…(3,26) This technique could also be extended in selected cases to include organic acidemias and hypercholesterolemia. (27,28) The recent report of successful auxiliary domino transplant from a child with propionic acidemia to correct Crigler-Najjar syndrome raises the possibility of organ exchanges between those with different metabolic diseases. (29) Some indications for transplantation have decreased with time.…”

First case of cross-auxiliary double domino donor liver transplantation

“…Liver transplantation has become a standard treatment for hereditary and metabolic liver diseases, such as familial amyloid polyneuropathy (FAP)[ 1 , 2 ]. Domino liver grafts from patients with some types of metabolic liver diseases, such as maple syrup urine disease[ 3 ] and methylmalonic acidemia[ 4 ], may function well in the recipient. Domino liver grafts are a good option for some recipients who might otherwise experience long wait times for liver transplantation, such as recipients with hepatocellular carcinoma (usually outside the Milan criteria)[ 5 ].…”