title: A detailed analysis of methylmalonic acid kinetics during hemodialysis and after combined liver/kidney transplantation in a patient with mut (0) methylmalonic acidemia.
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.
authors: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 733 N. Broadway, BRB 529, Baltimore, MD, 21205, USA, hvernon1@jhmi.edu.
authors: Hilary J
authors: HJ
authors: Vernon
authors: C John
authors: CJ
authors: Sperati
authors: Joshua D
authors: JD
authors: King
authors: Andrea
authors: A
authors: Poretti
authors: Neil R
authors: NR
authors: Miller
authors: Jennifer L
authors: JL
authors: Sloan
authors: Andrew M
authors: AM
authors: Cameron
authors: Donna
authors: D
authors: Myers
authors: Charles P
authors: CP
authors: Venditti
authors: David
authors: D
authors: Valle
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications*; D005260:Female; D006801:Humans; D007668:Kidney / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000628:therapy*; D016030:Kidney Transplantation; D007700:Kinetics; D008099:Liver / Q000601:surgery; D016031:Liver Transplantation; D008764:Methylmalonic Acid / Q000097:blood*; D008765:Methylmalonyl-CoA Mutase / Q000235:genetics; D011183:Postoperative Complications / Q000175:diagnosis*; D006435:Renal Dialysis
chemical_list: D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase