Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia

Abstract

Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but long-term 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 ± 1,968 preoperatively to 1,068 ± 384 mmol/mol creatinine) and plasma (from 445.9 ± 257.0 to 333.3 ± 117.7 μmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 ± 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 μmol/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.

Fig. 1

Human propionate metabolism. The three carbon groups of the metabolic sources of propionyl-CoA are shown in red. Enzymes are labeled (PCC propionyl-CoA carboxylase, and Mut methylmalonyl-CoA mutase, MMCE methylmalonyl-CoA epimerase). The acylcarnitine species are labeled according to their common designations (C3-acylcarnitine = propionylcarnitine, C4DC-acylcarnitine = methylmalonylcarnitine)

Fig. 2

Liver biopsy of explant from domino donor. Images (H&E stain, left: 40×, right: 400× magnification) show approximately 30% macrovesicular steatosis and an additional 10–20% microvesicular steatosis which is azonal, with focal ballooning degeneration and rare foci of lobular inflammation. There was no fibrosis identified on trichrome stain (not shown)

Fig. 3

Diet and laboratory results in the domino liver transplant donor. The shaded regions represent periods of hospitalization (see text). Note: methylmalonylcarnitine values are shown multiplied by 100 to facilitate viewing

Fig. 4

Diet and laboratory results in the domino liver transplant recipient. The shaded regions represent periods of hospitalization (see text). Note: methylmalonylcarnitine values are shown multiplied by 100 to facilitate viewing