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

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.
AuthorsHilary J Vernon, C John Sperati, Joshua D King, Andrea Poretti, Neil R Miller, Jennifer L Sloan, Andrew M Cameron, Donna Myers, Charles P Venditti, David Valle
JournalJournal of inherited metabolic disease (J Inherit Metab Dis) Vol. 37 Issue 6 Pg. 899-907 (Nov 2014) ISSN: 1573-2665 [Electronic] Netherlands
PMID24961826 (Publication Type: Case Reports, Journal Article)
Chemical References
  • Methylmalonic Acid
  • Methylmalonyl-CoA Mutase
  • Adult
  • Amino Acid Metabolism, Inborn Errors (complications)
  • Female
  • Humans
  • Kidney (surgery)
  • Kidney Failure, Chronic (therapy)
  • Kidney Transplantation
  • Kinetics
  • Liver (surgery)
  • Liver Transplantation
  • Methylmalonic Acid (blood)
  • Methylmalonyl-CoA Mutase (genetics)
  • Postoperative Complications (diagnosis)
  • Renal Dialysis

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