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A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut 0 methylmalonic acidemia

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Journal of Inherited Metabolic Disease

Abstract

End stage kidney disease is a well-known complication of methylmalonic acidemia (MMA), and can be treated by dialysis, kidney transplant, or combined kidney-liver transplant. While liver and/or kidney transplantation in MMA may reduce the risk of metabolic crisis and end-organ disease, it does not fully prevent disease-related complications. We performed detailed metabolite and kinetic analyses in a 28-year-old patient with mut 0 MMA who underwent hemodialysis for 6 months prior to receiving a combined liver/kidney transplant. A single hemodialysis session led to a 54 % reduction in plasma methylmalonic acid and yielded a plasma clearance of 103 ml/min and VD0.48 L/kg, which approximates the total body free water space. This was followed by rapid reaccumulation of methylmalonic acid over 24 h to the predialysis concentration in the plasma. Following combined liver/kidney transplantation, the plasma methylmalonic acid was reduced to 3 % of pre-dialysis levels (6,965 ± 1,638 (SD) μmol/L and 234 ± 100 (SD) μmol/L) but remained >850× higher than the upper limit of normal (0.27 ± 0.08 (SD) μmol/L). Despite substantial post-operative metabolic improvement, the patient developed significant neurologic complications including acute worsening of vision in the setting of pre-existing bilateral optic neuropathy, generalized seizures, and a transient, focal leukoencephalopathy. Plasma methylmalonic acid was stable throughout the post-operative course. The biochemical parameters exhibited by this patient further define the whole body metabolism of methylmalonic acid in the setting of dialysis and subsequent combined liver/kidney transplant.

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Authors and Affiliations

  1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 733 N. Broadway, BRB 529, Baltimore, MD, 21205, USA

    Hilary J. Vernon & David Valle

  2. Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

    C. John Sperati & Donna Myers

  3. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Joshua D. King

  4. Department of Emergency Medicine, University of Virginia, Charlottesville, VA, USA

    Joshua D. King

  5. Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA

    Andrea Poretti

  6. Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA

    Neil R. Miller

  7. NHGRI, National Institutes of Health, Bethesda, MD, USA

    Jennifer L. Sloan & Charles P. Venditti

  8. Department of Surgery, Johns Hopkins University, Baltimore, MD, USA

    Andrew M. Cameron

Authors
  1. Hilary J. Vernon
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  2. C. John Sperati
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  3. Joshua D. King
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  4. Andrea Poretti
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  5. Neil R. Miller
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  6. Jennifer L. Sloan
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  7. Andrew M. Cameron
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  8. Donna Myers
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  9. Charles P. Venditti
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  10. David Valle
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Correspondence to Hilary J. Vernon.

Additional information

Communicated by: Gerard T. Berry

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ESM 1

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Supplementary Table 1

CSF samples were taken on postoperative days operative days 28 (day of seizure onset) and 48 (day of seizure escalation), and from the CSF alone on day 55 (fever of unknown origin). All CSF samples had normal or negative protein, glucose, cell counts, and cultures (Supplementary Table 1) (GIF 237 kb)

(TIFF 29 kb)

Supplementary Table 2

Full Plasma and CSF amino acid profiles measured at post operative days (POD) 28, 48, 53 (CSF only), 55 (plasma only) and 57 (plasma only). All values are in uMol/L (GIF 268 kb)

(TIFF 54 kb)

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Vernon, H.J., Sperati, C.J., King, J.D. et al. A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut 0 methylmalonic acidemia. J Inherit Metab Dis 37, 899–907 (2014). https://doi.org/10.1007/s10545-014-9730-7

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  • DOI: https://doi.org/10.1007/s10545-014-9730-7

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