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.
Competing interests: None declared
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Acknowledgments
Supported in part by the National Institutes of Health Grants UL1TR000100 (BAB, WLN). We thank Dr. Grace Lin for the preparation and analysis of the histologic samples and Jon Gangoiti for the organic acid and acylcarnitine analyses.
Preliminary results from this study were presented orally at the Society for the Study of Inborn Errors of Metabolism Annual Symposium in Birmingham, England, 5 September, 2012.
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Communicated by: John H Walter, MD FRCPCH
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Details of the Contributions of Individual Authors
Dr. Bruce Barshop was responsible for the conception and planning of this project, did the majority of writing, and prepared the graphical figures.
Dr. Ajai Khanna was responsible for the conception and planning of this project, performed the surgery, and substantially contributed to the writing.
Dr. Robert Gish assisted in planning this project, performed medical management, and contributed to the writing.
Dr. Susan Winter provided clinical information and contributed to the writing.
Dr. William Nyhan assisted in planning this project and contributed to the writing.
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Khanna, A., Gish, R., Winter, S.C., Nyhan, W.L., Barshop, B.A. (2015). Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 25. JIMD Reports, vol 25. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_480
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