A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut0methylmalonic acidemia

Hilary 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

Research output: Contribution to journalArticle

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 mut0MMA 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.

Original languageEnglish (US)
Pages (from-to)899-907
Number of pages9
JournalJournal of Inherited Metabolic Disease
Volume37
Issue number6
DOIs
StatePublished - Oct 23 2014

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Methylmalonic Acid
Liver Transplantation
Kidney Transplantation
Renal Dialysis
Transplants
Kidney
Dialysis
Liver
Leukoencephalopathies
Optic Nerve Diseases
Body Water
Nervous System
Chronic Kidney Failure
Seizures

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut0methylmalonic acidemia. / Vernon, Hilary J; Sperati, C John; King, Joshua D.; Poretti, Andrea; Miller, Neil R; Sloan, Jennifer L.; Cameron, Andrew M; Myers, Donna; Venditti, Charles P.; Valle, David.

In: Journal of Inherited Metabolic Disease, Vol. 37, No. 6, 23.10.2014, p. 899-907.

Research output: Contribution to journalArticle

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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 mut0MMA 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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AU - Sperati, C John

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AU - Miller, Neil R

AU - Sloan, Jennifer L.

AU - Cameron, Andrew M

AU - Myers, Donna

AU - Venditti, Charles P.

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AB - 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 mut0MMA 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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